Tumor Ablation Instruments and Techniques

Abstract

Determine the tumor borders. A method for ablating a bordered tumor (15) in tissue of a subject includes advancing a distal region (200) of a tumor ablation device (102) into the tissue, the distal region having electrodes (2, 4) attached thereto. The bioimpedance of the tissue is then sensed using the distal region of the device. In response to the sensed bioimpedance, the electrodes are positioned within the border of the tumor. While the electrodes remain within the border, an electroporation pulse is applied to the tumor using the electrodes. Other embodiments are also described.

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, entitled "Adjustable electrode configurations for tumor ablation," filed May 22, 2021, which is incorporated herein by reference.

[0002] FIELD OF THEINVENTION The present 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 in 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 efficacy of this technique and concluded that changes in the electrical properties between the tumor and the surrounding tissue, together with inaccurate positioning of the electrodes, 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 boundaries. 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 boundaries, e.g., to focus treatment on tumor tissue rather than the surrounding tissue. It may be even more advantageous to position the treatment electrode near the tumor boundaries to treat the entire tumor - e.g., to avoid tumor cells near the tumor boundaries remaining untreated.

[0006] For some applications, it may be possible to determine the borders of a tumor by sensing bioimpedance due to differences in tissue properties between the tumor itself and its surrounding tissue. For example, healthy lung tissue generally has a high bioimpedance (e.g., due to the air-filled structure of the parenchyma and its alveoli), while lung tumors generally have a substantially lower bioimpedance. Therefore, bioimpedance sensing electrodes positioned near and / or within the tumor may be able to provide information regarding the borders of the tumor, particularly lung tumors. Furthermore, this difference in bioimpedance between the 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 the tumor compared to the surrounding tissue may facilitate conduction of the electroporation pulse throughout the tumor and not 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 into the patient transbronchially, for example, via 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 at its distal region. Once the distal region is positioned at the tumor, the tumor borders can be determined using the bioimpedance sensing electrodes. For some applications, due to differences in tissue properties between the 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 borders by moving (or facilitating the movement of) the bioimpedance sensing electrodes relative to the tumor and sensing the bioimpedance at different locations. For example, the bioimpedance sensing electrodes can be advanced into and / or out of the tumor so that the exact location of the transition (i.e., the border) between inside and outside can be identified. Based on the identified border, a treatment applicator (e.g., 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 therapeutic applicator is fixed and / or has a known position relative to the bio-impedance sensing electrodes such that once the tumor borders are determined, the therapeutic applicator is positioned just inside the tumor border. For some applications, the therapeutic applicator is automatically positioned within the tumor by determining the tumor borders using the bio-impedance sensing electrodes. For example, the device may be constructed such that by positioning the bio-impedance sensing electrodes at or just outside the tumor border, the device may automatically position the corresponding electroporation electrodes just inside the border. For some applications, once the tumor borders are determined, the surgeon may move the therapeutic applicator into and / or within the tumor using the known relative position between the therapeutic applicator and the bio-impedance sensing electrodes.

[0010] For some applications, bioimpedance sensing electrodes may be used to detect tumor boundaries and provide an alert, for example, indicating that further advancement is not required (or desired).

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

[0012] For some applications, bioimpedance sensing electrodes may be used to determine whether a lesion or growth is a cancerous tumor - for example, to facilitate diagnosis. For example, the bioimpedance of a cancerous tumor may be different 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 the 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 electrodes are located is lung tissue (e.g., lung parenchyma) rather than tumor tissue.

[0014] For some applications, the frequency of vibrations sensed at 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] Thus, 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] In general, some embodiments of the present disclosure include a device comprised 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 include one or more bioimpedance sensing electrodes.

[0018] In some embodiments, one or more electrodes (i.e., the inner electrode) are configured to pass through a second electrode (the 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, the 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 edge of the tumor.

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

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

[0028] Therefore, in accordance with 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 bio-impedance sensing electrode at a distal region and a treatment applicator adapted to ablate tumor tissue and to be positionally fixed at the distal region relative to the bio-impedance sensing electrode.

[0030] For some applications, the device includes a shaft on which the 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 a bioimpedance sensing electrode is placed outside the tumor and a treatment applicator is placed within the tumor. Progress is possible.

[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, proximal 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, 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 instrument is constructed 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 disposed 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 lung of the subject; and The device is configured to determine the boundaries of a lung tumor by sensing performed by bioimpedance sensing electrodes.

[0044] For some applications, the device includes a bronchoscope and can be advanced transbronchially to the lungs, and the shaft can be delivered 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 therapeutic applicator: an electroporation electrode; and The electrodes are adapted to apply an electroporation pulse 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 an electroporation electrode and a 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, the distal region being 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 in which a second electroporation electrode is disposed. a nested 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 at the distal portion, distal to the first electroporation electrode.

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

[0055] For some applications: the shaft is a first shaft, 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, at the distal region, the first shaft and the second shaft diverge relative to one another.

[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 can be bent 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 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 bio-impedance of tissue adjacent the bio-impedance 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 bio-impedance 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 controller is electrically connectable to the bio-impedance sensing electrodes by electrically connecting the controller to the terminals.

[0065] For some applications: The therapeutic applicator is configured to apply an electroporation pulse 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 therapeutic applicator is positionally fixed relative to the bioimpedance sensing electrodes, at a distance of 10 mm or less.

[0067] For some applications, the therapeutic 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 a tumor in the lung 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 borders of the tumor.

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

[0072] For some applications, the device includes a bronchoscope and can be advanced transbronchially to the lungs, and the shaft can be delivered 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 an electroporation electrode and a bioimpedance sensing electrode.

[0084] For some applications: the electroporation electrode is a first electroporation electrode; The device further includes 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, 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, at a distal region of the instrument, the first shaft and the second shaft diverge relative to one another.

[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 disposed 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 can be bent 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 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 bio-impedance of tissue adjacent to the bio-impedance 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 a position of the bio-impedance 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 controller is electrically connectable to the bio-impedance sensing electrodes by electrically connecting the controller 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 less than 10 mm.

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

[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, the second shaft being a shaft of the second instrument.

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

[0104] For some applications, electrodes are positioned within the boundaries of a 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 boundary.

[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 disposed on a 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 borders of the tumor involves moving a distal region of the device through the tumor until the bioimpedance sensing electrodes exit the tumor.

[0110] For some applications: Sensing bioimpedance using the bioimpedance sensing electrodes includes sensing bioimpedance using 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; and Positioning the electrode within a 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 a 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 being 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 an 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, subsequent to applying an electroporation pulse, 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 a fixed position relative to the first bioimpedance sensing electrode; Includes.

[0119] For some applications, the distal region further comprises 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 portion and the second portion.

[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, at the distal region, the first shaft and the second shaft diverge relative to one another.

[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 through 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 disposed on the first shaft distal to the first electroporation electrode.

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

[0128] For some applications, a first bioimpedance sensing electrode is disposed 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 can be bent relative to the second shaft.

[0131] Further, in accordance with 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 borders of the tumor.

[0133] Further, 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 disposed axially 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, a method for ablating a tumor is provided, the method including: 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, actuating the electroporation electrode to apply a first electroporation pulse to the tumor.

[0137] For some applications, the method further includes determining a 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, actuating the electroporation electrode to apply a second electroporation pulse to the tumor.

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

[0140] For some applications, actuating the electroporation electrode to apply a first electroporation pulse to the tumor includes actuating 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 may include: 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 may include: determining whether the magnitude of the vibration is above 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 a frequency of vibration of a portion of a respiratory cycle.

[0147] Further, in accordance with 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, in accordance with 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 with an electroporation electrode attached; 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 comprises: distal advancement of the outer shaft over the inner shaft progressively covering 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 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 bio-impedance of tissue adjacent the bio-impedance 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 bio-impedance 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 controller is electrically connectable to the bio-impedance sensing electrodes by electrically connecting the controller to the terminals.

[0158] Further, according to some applications, a method for ablating a tumor is provided, the method including: advancing a distal region of a tumor ablation device into a tumor, the device comprising: an inner shaft having an electroporation electrode attached thereto; and An outer shaft adapted to slide over the inner shaft Contains 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 actuating 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 electrodes includes adjusting the effective length guided by sensing performed by the bioimpedance sensing electrodes.

[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 bio-impedance sensing electrodes includes adjusting the effective length guided by sensing performed by the bio-impedance sensing electrodes while the bio-impedance sensing electrodes are electrically connected to a controller, the controller being configured to provide an alert in response to a change in bio-impedance detected by the bio-impedance sensing electrodes upon exit of the bio-impedance 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, taken in conjunction with the drawings. [Brief description of the drawings]

[0170] BRIEF DESCRIPTION OF THE DRAWINGS [Figure 1] 1 is a schematic diagram of an apparatus for electroporation ablation, according to some embodiments of the present disclosure. [Diagram 2] 1 is a schematic diagram of an apparatus for electroporation ablation guided by bioimpedance sensing according to some embodiments of the present disclosure. FIG. [Diagram 3] 1 is a schematic diagram 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. [Diagram 5] 1 is a schematic diagram 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] 1 is a schematic diagram of an apparatus for electroporation ablation guided by bioimpedance sensing according to some embodiments of the present disclosure. FIG. [Figure 11A] 1 is a schematic diagram of an apparatus for electroporation ablation guided by bioimpedance sensing according to some embodiments of the present disclosure. FIG. [Figure 11B] 1 is a schematic diagram of an apparatus for electroporation ablation guided by bioimpedance sensing according to some embodiments of the present disclosure. FIG. [Figure 11C] 1 is a schematic diagram of an apparatus for electroporation ablation guided by bioimpedance sensing according to some embodiments of the present disclosure. FIG. [Figure 12] 1 is a schematic diagram of an apparatus for electroporation ablation guided by bioimpedance sensing according to some embodiments of the present disclosure. FIG. [Figure 13A] 1 is a schematic diagram of an apparatus for electroporation ablation guided by bioimpedance sensing according to some embodiments of the present disclosure. FIG. [Figure 13B] 1 is a schematic diagram of an apparatus for electroporation ablation guided by bioimpedance sensing according to some embodiments of the present disclosure. FIG. [Figure 13C] 1 is a schematic diagram of an apparatus for electroporation ablation guided by bioimpedance sensing according to some embodiments of the present disclosure. FIG. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

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

[0172] For some applications, it may be possible to determine the borders of a tumor by sensing bioimpedance, due to differences in tissue properties between the tumor itself and its surrounding tissue. For example, healthy lung tissue generally has a high bioimpedance (e.g., due to the air-filled structure of the parenchyma and its alveoli), while lung tumors generally have a substantially lower bioimpedance. Therefore, bioimpedance sensing electrodes positioned near and / or within the tumor may be able to provide information regarding the borders of the tumor, particularly lung tumors. Furthermore, this difference in bioimpedance between the 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 the tumor compared to the surrounding tissue may facilitate the conduction of the electroporation pulse throughout the tumor, and not into the surrounding tissue.

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

[0174] As shown in FIG. 1, the instrument 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 through which they are guided to access the tumor. For some applications, as shown in FIG. 6A-D, the instrument 101 is advanced into the patient's body, e.g., into the patient's lungs 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., via 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 into the parenchyma adjacent to the tumor. For some such applications, the shaft 1 may be flexible. For some applications, advancement is performed percutaneously (eg, transluminally or transthoracically). For some such applications, the shaft 1 may be rigid.

[0175] A first electroporation electrode 4 is disposed at 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 causes the electrode 4 to also be advanced into the tumor. For some embodiments, a second electroporation electrode 2 may also be disposed at the distal region 100 - e.g., also positioned within the tumor such 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 can be reversibly lengthened to vary the axial distance L between the electrodes 2 and 4. For some applications, the distal region 100 can include a telescoping assembly - for example, 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 can be defined by a distal portion of the shaft 3. The proximal portion 12 can be defined by a distal portion of the shaft 1.

[0177] For some such applications, shafts 1 and 3 are coaxial. As explained above, in order 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) to adjust the distance L between the electrodes.

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

[0179] Reference will now be made to FIG. 2 and FIG. 6A-D, which are schematic illustrations of a system 2000 for electroporation ablation of a tumor 15, according to some applications. The system 2000 includes an instrument (e.g., device) 102, and may further include a controller 2010. The controller 2010 may include a generator (or power source) 7a. Similar to the instrument 101, the instrument 102 may include at least one shaft 1 (e.g., a flexible tube, catheter, rod, and / or bronchoscope) and has a distal region 200 adapted to be advanced into the tumor 15. Also similar to the instrument 101, a first electroporation electrode 4 and a second electroporation electrode 2 are disposed in the 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 bio-impedance sensing electrodes at its distal region 200, such as a first bio-impedance sensing electrode 8 and a second bio-impedance sensing electrode 9. For some applications, these bio-impedance 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 bio-impedance sensing electrodes described herein has been described and referred to as a single electrode, any of these bio-impedance sensing electrodes may in fact represent a set of electrodes that may work together - for example to function as a bio-impedance sensor (e.g., further working with the controller 2010). That is, for some applications, any of the bio-impedance sensing electrodes described herein may be comprised of two or more (e.g., a plurality) electrodes. For some such applications, such a bio-impedance sensing electrode (including a plurality of individual electrodes) may be considered to be a bio-impedance 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 the 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) - as described for device 101, for example. In addition, device 102 will generally also include 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, the bioimpedance sensing is performed in a constant potential mode. For some applications, the bioimpedance sensing is performed in a constant current mode. For some applications, the current used to perform the bioimpedance sensing is a low voltage (e.g., at least 0.5V and / or 5V or less) current. For some applications, the current used to perform the bioimpedance sensing has a sinusoidal waveform. For some applications, the current used to perform the bioimpedance sensing has a frequency of at least 10 Hz and / or 1 MHz or less. For some applications, the current used to perform the bioimpedance sensing has an amplitude of at least 1 microamp and / or 15 milliamp or less.

[0185] Once the distal region 200 has been advanced to the tumor 15, the borders of the tumor may be determined using the bio-impedance sensing electrodes 8 and 9. For example, as described above, due to, for example, differences in tissue properties between a tumor and its surrounding tissue, the device (e.g., its controller 2010) may determine (or facilitate the determination of) the borders of the tumor by moving (or facilitating the movement of) the bio-impedance sensing electrodes 8 and 9 relative to the tumor and sensing bio-impedance at different locations. For example, as shown diagrammatically in Figures 6A-D, the bio-impedance sensing electrodes may be advanced into and / or out of the tumor so that the exact location of the transition (i.e., boundary) between inside and outside may be identified - for example, by determining whether each of the bio-impedance sensing electrodes 8 and 9 is disposed 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 ground 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 are used in a monopolar fashion), and the controller 2010 may 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, the electrode 8 or electrode 9 may be replaced by a skin electrode or a ground 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, for example, 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 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 a 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 border (e.g., a map showing the tumor border) may be output by the controller to enable the surgeon to position one or more electroporation electrodes within the border. For some applications, the output is discrete, e.g., a text output representing the tissue type that is determined to be within which the bioimpedance sensing electrodes (and / or electroporation electrodes) are to be placed.

[0191] The 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, to automatically position (or facilitate positioning) the therapeutic applicator just inside the tumor boundary by positioning the electrodes 8 and 9 just outside the tumor boundary. For example, as shown in FIG. 2 and FIG. 6A-D, by virtue of an arrangement in which the electroporation electrodes 2 and 4 are axially positioned between the bioimpedance sensing electrodes 8 and 9, by establishing that the bioimpedance sensing electrodes are at (e.g., just outside) the tumor 15 boundary, the device 102 can automatically demonstrate that the 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) of the tumor boundary, e.g., within 0.5-5 mm of the boundary. For some applications, a similar technique may be used such 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, the distal region 200 may include a nested assembly - e.g., having a distal portion 24 (which may be a distal portion of shaft 3) and a proximal portion 22 (which may be a 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, the electroporation electrode 4 is disposed on the distal portion 24, and the bioimpedance sensing electrode 9 is disposed on the distal portion just distal - 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 - from the electroporation electrode 4, such that positioning of the bioimpedance sensing electrode 9 just beyond the tumor border positions the electroporation electrode 4 just inside the border. That is, electrode 4 becomes positioned on the opposite side of the border from electrode 9, with the border being between the electrodes. Thus, the bioimpedance sensing electrode 9 may 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), e.g., indicating that further distal advancement is not needed (or desired). Similarly, the second electrode 2 is positioned at the proximal portion 22, and the bioimpedance sensing electrode 8 is positioned at the proximal portion just proximal to the electroporation electrode 2, 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, such that positioning of the bioimpedance sensing electrode 8 just before (e.g., proximally therefrom) the tumor boundary positions the electroporation electrode 2 just inside 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 opposing 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. It should be noted that Figures 6A-D are intended primarily to illustrate the capabilities of system 2000, rather than strictly defining a sequence of procedural steps.

[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 bio-impedance sensing electrode 9 exits the tumor - e.g., the distal border of the tumor (FIG. 6B). For example, the controller 2010 may provide an alert to the surgeon in response to a change in bio-impedance detected by the electrode 9 as it exits the tumor 15. As explained above, this positioning of the bio-impedance sensing electrode 9 just outside the tumor border positions the electroporation electrode 4 just inside the border. 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., distance L, discussed above) is short enough such that the positioning of electrode 4 just inside the distal border of the tumor positions both the electroporation electrode 2 and the bio-impedance 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 dimensions 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., telescopically withdrawing proximal portion 22 of the distal region from distal portion 24) to position electrode 2 just inside the proximal border 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 border of the tumor positions electroporation electrode 2 just inside the border.

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

[0198] For some applications, the controller 2010 is adapted to adjust the electroporation pulses applied by the generator 7a in response to bioimpedance sensing. For example, the controller 2010 may be adapted to monitor the progress of the treatment by monitoring changes in the impedance of the tumor 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 further 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 an 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 telescopically 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 is inserted at a different angle.

[0202] In some embodiments, multiple shafts (e.g., multiple instances of shafts 3), each having an electroporation electrode, may be passed (e.g., simultaneously) through shaft 1. For some applications, each shaft 3 has a bioimpedance sensing electrode mounted thereon to provide information regarding its respective electroporation electrode relative to the boundaries of the tumor, 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 full coverage of the area.

[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 variant 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 control device, such as control device 2010. As with 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. As with the devices described above, a first electroporation electrode 4 is disposed at the distal portion, and a second electroporation electrode 2 is disposed at the proximal portion. As described with reference to device 102 above, bioimpedance sensing electrodes may be disposed at 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, so that electrode 4 can be oriented at an angle relative to electrode 2 within the tumor. 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 is now made to FIG. 5, which is a schematic diagram of a device 104 for tumor ablation according to some embodiments of the present disclosure. Device 104 may be considered a variation of device 101 and / or device 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. As with the devices described above, a first electroporation electrode 404 is disposed on the distal portion, and a second electroporation electrode 402 is disposed on the proximal portion. Bioimpedance sensing electrodes may be disposed on each of the distal and proximal portions, respectively, as described with reference to device 102 above. Also, similar to the devices described above, 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 instrument 104 may be similar to those described above, but 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 and the electrode 404 may 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 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 the 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 is also disposed with a bioimpedance sensing electrode to determine, for example, whether the electroporation electrode in that distal region is located within the tumor, but at the border of the tumor. Having two or more distal regions may advantageously allow for positioning electroporation electrodes at various borders of the tumor, ensuring full coverage of the tumor's extent. For example, Figures 7-9B may be understood as such devices having two or more distal regions for positioning electroporation electrodes.

[0209] 7 shows a system 7000 including multiple devices 102, each having at least one electroporation electrode disposed thereon, advanced into a tumor 15. Each of the devices 102 may 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 instrument 108. System 8000 may otherwise be identical to system 7000, except that the instrument 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 various 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 a distal region 19, at which each electroporation electrode 20 is located, into the tumor 15 from various access points or particular angles or interests. Each steerable catheter 18 can be advanced into the tumor from a different airway (e.g., bronchus) such that opposing and / or spaced borders 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 borders of the tumor.

[0212] 9B, an otherwise identical device 109' has a bioimpedance sensing electrode 26 disposed 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 an electroporation electrode 20 disposed at its distal region 19, thereby identifying that the bioimpedance sensing electrode 26 is disposed just outside the tumor 15, thereby providing confirmation that the electrode 20 is just inside the tumor boundary - e.g., as described above, mutatis mutandis.

[0213] Reference will now be made to Figures 10 and 11A-C, which are schematic diagrams 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, such as system 2000, and / or may be compatible with a controller, such as 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, which is 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 electroporation pulses 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 to enable 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] As shown by Figures 11A-C, the distal region 500 may be advanced into the tumor 15 until the bio-impedance sensing electrode 29 exits the tumor - e.g., the distal border of the tumor (Figure 11A). For example, the controller may provide an alert to the surgeon in response to a change in bio-impedance detected by the electrode 29 as the electrode exits the tumor 15. As described above in connection with Figures 6A-D, this positioning of the bio-impedance sensing electrode 29 just outside the border of the tumor positions the electroporation electrode 21 just inside the border. While the electroporation electrode 21 is positioned at the border, electroporation pulses may be applied to the tumor to ablate at least a peripheral portion of the tumor.

[0216] 11B shows the distal region 500 having been moved part way 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 may be used to detect the tumor border and to alert the surgeon once the electroporation electrodes have reached the opposing (e.g., proximal) border of the tumor (FIG. 11C), which may 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, such as system 2000, and / or may be compatible with a controller, such as 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, an additional bioimpedance sensing electrode 30 is positioned between electroporation electrodes 21. Bioimpedance may 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 several applications.

[0221] The device 113 may be considered a variation of any of the devices described above and 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, the device 113 has a distal region 700 adapted to be advanced into a tumor. The device 113 includes an electroporation electrode 44 at the distal region - for example, may include only a single electroporation electrode. The device 113 is configured to facilitate adjustment of the effective length of the electroporation electrode 44 - for example, according to the size of the tumor. A remote electrode (e.g., remote electrode 40 or the like, such as a skin electrode or ground pad) may be used to facilitate delivery of the electroporation pulse to the tumor - for example, with the remote electrode functioning as a return electrode.

[0222] For some such applications, the distal region 700 includes a nested 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, the instrument 113 includes an outer shaft 701 and an inner shaft 703 adapted to slide into and / or out of the distal end of the shaft 701. The 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 the shaft 703 functions as the distal portion 724 and the distal region of the shaft 701 functions as the 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 within 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 such that 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 disposed on the proximal portion 722, e.g., at the distal end of the shaft 701, and a second bioimpedance sensing electrode 9 is disposed on the distal portion 724, e.g., distal to the electrode 44. For such applications, such placement of the bioimpedance sensing electrodes on the side of the 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 of the distal region 700, and thereby an appropriate effective length of the electrode 44 - e.g., by providing an alert once the appropriate length is achieved. For some applications, and as illustrated, the device 113 is configured such that, at the appropriate length, the electroporation electrode 44 spans most of the length of the tumor (i.e., most of the distance between the distal border of the tumor and the proximal border of the tumor) - e.g., substantially the entire length of the tumor.

[0225] As shown by FIGS. 13A-C, the distal region 700 can be advanced into the tumor 15 until the bioimpedance sensing electrode 9 exits the tumor, e.g., the distal border of the tumor (FIG. 13A). For example, the controller can provide an alert to the surgeon in response to a change in bioimpedance detected by the electrode 9 as it exits the tumor 15. Similar to that described above in connection with FIGS. 6A-D, this positioning of the bioimpedance sensing electrode 9 just outside the border of the tumor positions the distal end of the electroporation electrode 44 just inside the border. In this state, the electroporation electrode 44 may not yet have a desired effective length. Therefore, the proximal portion 722 is then withdrawn proximally from the distal portion 724 (e.g., by sliding the shaft 701 proximally along the shaft 703), thereby exposing more of the 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-sectional view through a shaft 1 according to some applications.

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

[0229] In some embodiments, hollow shaft 1 is constructed of an additional layer of braid and a polymer tube. Advantageously, the additional layer may be used to transmit a signal from bioimpedance sensing electrode 8. For example, braid 13 may function as a conductor for electrode 2, while the additional layer of braid may 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, 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 as 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 and electrical signals sent from the proximal terminal to the electrodes using conductive wires are passed through it, hi some embodiments, the shaft may be constructed from a metallic tube or multiple metallic tubes partially covered with an insulating layer or layers.

[0235] In some embodiments, the signal from the bioimpedance sensing electrodes 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 is insulated from 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 to the controller 1010 regarding the bioimpedance sensed at the tumor in order to provide the controller with information regarding 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, another type of therapeutic applicator 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 drugs), caustic agents (e.g., ethanol), cryogenic fluids, or radiation sources. For some applications, such another therapeutic applicator is used in place of the electroporation electrode. For some applications, such another therapy is used in combination with the electroporation electrode - e.g., to provide a synergistic effect. For some such applications, the therapeutic applicator for such additional therapy is coupled to and / or advanced through the outer shaft of the device. For other such applications, the therapeutic applicator for such additional therapy is 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 may be at least 1 mm (eg, at least 2 mm) and / or no more than 50 mm (eg, no more than 20 mm, eg, no more than 10 mm).

[0242] In some embodiments, the length of each bio-impedance 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 electric 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, such as 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 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, such as 1-3 MHz, such as 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 200V (e.g. at least 500V, e.g. at least 2000V) and / or 1000V or less (e.g. 500V or less) - e.g. 200-500V. 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 therebetween (where the pulses may have the characteristics and spacing described below). For some applications, each train comprises 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 the 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 a percutaneous device, described as the length between the proximal terminal and the electrode, may be, for example, at least 10 cm and / or up to 50 cm, e.g., between 15 cm and 50 cm.

[0253] In some embodiments, the electrode is configured to be delivered through a bronchoscope. 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 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, 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 application 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 - for example, 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 the 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 electrodes are located is lung tissue (e.g., lung parenchyma) rather than tumor tissue.

[0260] For some applications, the frequency of vibrations sensed at 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 that includes:

[0262] Tumor ablation is given as an example of one use of the device, however 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] It should be noted 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 the 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 use with a tumor within a subject, the apparatus comprising a tumor ablation device having a distal region, the tumor ablation device comprising: An inner shaft; an outer shaft with which the inner shaft is coaxially disposed, The inner shaft comprises: a first bioimpedance sensing electrode; a first electroporation electrode attached at a fixed location proximal from the first bioimpedance sensing electrode; The outer shaft comprises: a second bioimpedance sensing electrode; a second electroporation electrode attached at a fixed location distal to the second bioimpedance sensing electrode; The device, wherein the inner shaft and the outer shaft are telescopically slidable relative to one another to vary a first axial distance between the first electroporation electrode and the second electroporation electrode.

2. The device of claim 1 , wherein the tumor is a tumor in the subject's lung and the distal region is transbronchially deliverable to the lung.

3. 2. The device of claim 1, wherein the tumor has a boundary, and the distal region is advanceable to a position within the lung by telescopically sliding the inner shaft and the outer shaft relative to one another, where the first electroporation electrode and the second electroporation electrode are both positioned within the boundary of the tumor, and the first bioimpedance sensing electrode and the second bioimpedance sensing electrode are both positioned outside the boundary of the tumor, on opposite sides of the tumor.

4. 2. The device of claim 1, configured to sense bioimpedance in the tumor by sensing bioimpedance between the first electroporation electrode and the first bioimpedance sensing electrode and bioimpedance between the second electroporation electrode and the second bioimpedance sensing electrode.

5. 2. The device of claim 1, configured to sense bioimpedance at the tumor by sensing bioimpedance between the first bioimpedance sensing electrode and the second bioimpedance sensing electrode.

6. The device of claim 1 , wherein the inner shaft is advanceable from a distal end of the outer shaft.

7. 10. The device of claim 1, further comprising a control unit including a generator electrically connectable to both the first electroporation electrode and the second electroporation electrode and adapted to drive electroporation pulses therebetween.

8. The device of claim 1 , wherein the outer shaft is formed from an electrical insulator.

9. The device of claim 8 , configured to allow an effective length of the first electroporation electrode to be adjusted by sliding the outer shaft over the first electroporation electrode.

10. 2. The device of claim 1, comprising a control unit configured to receive a signal from the first bioimpedance sensing electrode and responsively provide an output indicative of the bioimpedance of tissue adjacent to the first electroporation electrode, and to receive a signal from the second bioimpedance sensing electrode and responsively provide an output indicative of the bioimpedance of tissue adjacent to the second electroporation electrode.

11. The apparatus of claim 10 , wherein the control unit is configured to output information indicative of a position of each of the first and second electroporation electrodes relative to the tumor in response to a signal.

12. 11. The device of claim 10, wherein the control unit is configured to, in response to a signal, determine whether a state of the distal region is such that both the first electroporation electrode and the second electroporation electrode are disposed within a tumor, and in response to determining that the distal region is such, provide an indication that both the first electroporation electrode and the second electroporation electrode are disposed within a tumor.

13. The apparatus of claim 10 , wherein the control unit is configured to generate a signal by driving an electrical pulse between the first and second bio-impedance sensing electrodes.

14. 11. The device of claim 10, wherein the control unit is configured to receive a signal by driving a first electrical pulse between the first electroporation electrode and the first bioimpedance sensing electrode and driving a second electrical pulse between the second electroporation electrode and the second bioimpedance sensing electrode.

15. 11. The apparatus of claim 10, wherein the control unit is configured to output information indicative of a position of the first bio-impedance sensing electrode and the second bio-impedance sensing electrode relative to the tumor in response to a signal.

16. 16. The device of claim 15, wherein the control unit is configured to, in response to a signal, distinguish a state of the distal region in which both the first bioimpedance sensing electrode and the second bioimpedance sensing electrode are located outside a tumor from one or more other states of the distal region in which at least one of the first bioimpedance sensing electrode and the second bioimpedance sensing electrode are located inside a tumor, and in response to the distinction, provide an indication that the distal region is in that state.

17. 16. The device of claim 15, wherein the control unit is adapted, in response to the signal, to distinguish between (i) a condition of the distal region where both the first bioimpedance sensing electrode and the second bioimpedance sensing electrode are located outside a tumor and (ii) one or more other conditions of the distal region where at least one of the first bioimpedance sensing electrode and the second bioimpedance sensing electrode is located inside a tumor, and, in response to the distinction, to provide an indication of whether the first electroporation electrode and the second electroporation electrode are positioned within the tumor.

18. 2. The apparatus of claim 1, wherein the tumor is disposed in a lung of the subject, and the apparatus is configured to determine a boundary of the tumor by sensing bioimpedance via at least one of the first bioimpedance sensing electrode and the second bioimpedance sensing electrode.

19. 20. The apparatus of claim 18, comprising a bronchoscope, the bronchoscope being transbronchially advanceable to the lungs, and the distal region being deliverable via the bronchoscope to the tumor.

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