Endoscopic electroporation of tissue

Abstract

A system (20) for endoscopic electroporation of tissue, particularly for tumor ablation, includes (i) a tool (100) comprising an extracorporeal proximal region (102) and an intracorporeal distal region (104), and (ii) a control unit (500). The tool comprises a pair of shafts (220, 420) configured for relative axial movement, and with electrode assemblies (310, 410) disposed thereon. The electrode assemblies are configured to measure bioimpedance of surrounding tissue for precise positioning within a tumor, and to deliver electroporation pulses for ablation. The control unit is operable in a positioning mode to detect tumor boundaries based on impedance, and in an electroporation mode to apply high-voltage pulses between electrodes formed by proximal and distal electrodes. Other embodiments are also described.

Description

SNP1010-W001ENDOSCOPIC ELECTROPORATION OF TISSUECROSS-REFERENCES TO RELATED APPLICATIONS

[0001] The present application claims priority to Provisional US Patent Application 63 / 773,606 to Omri et al., filed 18 March 2025, and titled "Endoscopic electroporation of tissue," which is incorporated herein by reference.FIELD OF THE INVENTION

[0002] The present application relates to the field of medical devices, particularly devices for tumor ablation.BACKGROUND

[0003] Electric field pulses of high intensity and short duration can cause tissue ablation in a process called irreversible electroporation (IRE). IRE has been described in the art for treatment of tumors in various locations in the body and most commonly inserted percutaneously.

[0004] J. Rieke et al. (The ALICE Trial, Cardiovascular and Interventional Radiology (2015) 38:401-408) have described the use of IRE for percutaneous treatment of lung tumors. The authors failed to demonstrate the efficacy of this technique, with the conclusion that the variance in electric properties between the tumor and surrounding tissue together with inaccurate positioning of the electrodes caused improper electric field distribution inside the target tissue.SUMMARY OF THE INVENTION

[0005] This summary is meant to provide some examples and is not intended to be limiting of the scope of the invention in any way. For example, any feature included in an example of this summary is not required by the claims, unless the claims explicitly recite the features. Also, the features, components, steps, concepts, etc. described in examples in this summary and elsewhere in this disclosure can be combined in a variety of ways. Various features and steps as described elsewhere in this disclosure may be included in the examples summarized here.

[0006] Any of the techniques, methods, operations, steps, etc. described or suggested herein can be performed on a living animal (e.g., human, other mammal, etc.) or on a non-livingSNP1010-W001simulation such as a cadaver, a cadaver heart, an anthropomorphic ghost, and / or a simulator device (which may include computerized and / or physical representations of body parts, tissue, etc.).

[0007] In accordance with some implementations, a system is provided that is configured to electroporate tumor cells in the lungs of a subject or in any other suitable tissue. That is, the surrounding tissue and the tumor should have a large bioimpedance difference between them.

[0008] In order to electroporate, the system may include electroporation electrodes to apply a electromagnetic pulse. These electrodes may be positioned inside the tumor such that the electromagnetic field will cover as much of the tumor as possible. Therefore, the system may include two more electrodes as well to be used as sensors to locate the boundaries of the tumor. Using these sensing electrodes, the electroporation electrodes may be positioned inside the tumor, as close to the boundaries of the tumor as possible.

[0009] The system may include two shafts upon which the electrodes are mounted. Each of the shafts may include, at a distal region, one electroporation electrode and one sensory electrode. One of the shafts (i.e. a second shaft) may allow the other shaft (i.e. a first shaft) to advance through it. Both shafts may advance within a sheath. The sheath and shafts may be transbronchially advanced to the vicinity of the tumor, e.g. using an endoscope. The advancement may be performed by manipulating a handle assembly that includes a sheath stock, a first-manipulator stock, and / or a second-manipulator stock for the sheath and the first and second shafts, respectively.

[0010] In accordance with some implementations, a system for treating a tumor in a subject comprises (i) a tool having an extracorporeal proximal region and an intracorporeal distal region; (ii) at the distal region, a proximal electrode assembly and a distal electrode assembly, the proximal electrode assembly including a first proximal electrode and a second proximal electrode fixedly spaced on a first, telescoping shaft, and the distal electrode assembly including a first distal electrode and a second distal electrode fixedly spaced on a second, telescoping shaft; (iii) a telescopic arrangement in which the second shaft is extendible distally from the first shaft so as to vary an axial spacing between the proximal and distal electrode assemblies; and / or a control unit located at or near the extracorporeal proximal region and electrically connected to all four electrodes, the control unit being configured to operate in (i) a positioning mode for measuring bioimpedance between electrodes to detect when the distal region has reached a desired treatment position, and (ii)SNP1010-W001an electroporation mode for delivering one or more electroporation pulses between electrodes once that treatment position is confirmed.

[0011] In some implementations, the tool is manipulated between: (a) a provisional position in which at least one of the first proximal electrode or the first distal electrode resides within the tumor, and (b) a treatment position in which both first electrodes lie outside the tumor while both second electrodes lie within the tumor.

[0012] In some implementations, the control unit’s positioning mode configures a first bioimpedance circuit between the first proximal electrode and the second proximal electrode; measures their impedance to determine tumor boundary contact; and, optionally, configures a second bioimpedance circuit between the first distal electrode and the second distal electrode for redundant confirmation.

[0013] In certain implementations, upon verifying the proper interleaving of electrodes positioned internally and externally relative to the tumor, the control unit transitions to the electroporation mode by configuring (i) the first and second proximal electrodes to be electrically connected in parallel, thereby forming a proximal electroporation electrode, and (ii) the first and second distal electrodes to be electrically connected in parallel, thereby forming a distal electroporation electrode, followed by the delivery of one or more high-voltage electroporation pulses between these two composite electrodes.

[0014] In accordance with some implementations, the control unit further (i) receives a start signal and an interelectrode distance value indicative of the axial spacing between electrode assemblies; (ii) sets a voltage ceiling for a pulse application routine based on that interelectrode spacing; and / or executes a dynamic pulse subroutine in which the system delivers a series of electroporation pulses, each pulse having a voltage that increases (subject to the ceiling) or decreases responsively to a measured pulse current versus a predefined current threshold; • Determines a steady-state voltage either when a pulse’s voltage reaches the maximum limit or when the measured current falls within a predefined threshold range; and • Executes a steady-state subroutine that delivers additional pulses all at that steady-state voltage.

[0015] In some implementations, the control unit is further configured to (i) limit the total number of delivered pulses (dynamic plus steady) to a preset maximum; (ii) synchronize each pulse to the patient’s heartbeat so that one pulse is delivered per cardiac cycle; and / orSNP1010-W001generate a recommendation — based on the tumor’s geometry and prior pulse efficacy — to adjust the electrode spacing or to repeat the routine under the same or a new configuration.

[0016] In some implementations, the control unit is configured to verify adequate electrical coupling between the proximal electrode assembly and the distal electrode assembly during execution of the dynamic pulse subroutine by determining whether tissue between the electrode assemblies supports a pulse current greater than a current floor. In some such implementations, the control unit determines that adequate electrical coupling has failed when two or more consecutive pulses, such as three or more consecutive pulses, have measured currents below the current floor and, responsive thereto, stops the dynamic pulse subroutine, aborts the pulse application routine, and outputs a notification to an operator to prompt repositioning of one or both electrode assemblies before another pulse application routine is attempted. In some implementations, the current floor is 0.5 A.

[0017] In some implementations, the first and second shafts include radiopaque markers and the tool’s design provides a radiolucent window between proximal electrodes. This arrangement permits fluoroscopic confirmation of the correct interelectrode distance: a radiopaque tubular structure on the second shaft vacates the radiolucent window precisely when the predefined spacing is attained, thereby guiding exact positioning prior to electroporation.

[0018] In some implementations, the tool is dimensioned and configured for transbronchial delivery into a lung tumor, using an introducer sheath and endoscopic guidance, with adjustable set-screws or pins to lock the shafts once the desired positions are reached.

[0019] There is further provided, in accordance with some implementations, a system for use with a tumor within a subject, the system including a tool and / or a control unit.

[0020] The tool may have an extracorporeal proximal region and a distal region, and may include, at the distal region:a proximal electrode assembly, including:a first proximal electrode, mounted on a first shaft of the tool, and / or a second proximal electrode, mounted on the first shaft at a fixed position distally from the first proximal electrode; and / ora distal electrode assembly, including:a first distal electrode, mounted on a second shaft of the tool, and / orSNP1010-W001a second distal electrode, mounted on the second shaft at a fixed position proximally from the first distal electrode, wherein:the first shaft and the second shaft are telescopically arranged such that the second shaft is telescopically extendible distally from the first shaft in a manner that changes an axial distance between the distal electrode assembly and the proximal electrode assembly, and / orthe tool is operable to manipulate the distal region between (a) a provisional position in which at least one of the first proximal electrode and the first distal electrode is disposed within the tumor, and (b) a treatment position in which (i) the first proximal electrode and the first distal electrode are both disposed outside of the tumor, and (ii) the second proximal electrode and the second distal electrode are both disposed within the tumor; and / or

[0021] The control unit may be connectable to the proximal region of the tool to electrically connect the control unit to the first and second electrode assemblies, and, while electrically connected to the first and second electrode assemblies, configured to:switch between:a positioning mode in which the system defines a positioning circuit in which the first proximal electrode and the second proximal electrode are in series with each other, and / oran electroporation mode in which the system defines an electroporation circuit in which (i) the first distal electrode and the second distal electrode are in parallel with each other to collectively define a distal electroporation electrode, and (ii) the first proximal electrode and the second proximal electrode are in parallel with each other to collectively define a proximal electroporation electrode that is in series with the distal electroporation electrode,in the positioning mode, identify, via measurement of bioimpedance between the first proximal electrode and the second proximal electrode, whether the distal region is in the treatment position, and / orwhile the distal region is in the treatment position, drive an electroporation pulse between the proximal electroporation electrode and the distal electroporation electrode.

[0022] In some implementations:the positioning circuit is a first positioning circuit,SNP1010-W001in the positioning mode the system further defines a second positioning circuit in which the first distal electrode and the second distal electrode are in series with each other, and / orthe control unit is configured, in the positioning mode, to identify whether the distal region is in the treatment position via (i) measurement of bioimpedance between the first proximal electrode and the second proximal electrode, and (ii) measurement of bioimpedance between the first distal electrode and the second distal electrode.

[0023] There is further provided, in accordance with some implementations, a system for use with a tumor within a subject, the system including:a tool that has an extracorporeal proximal region and a distal region, and that includes, at the distal region:a proximal electrode assembly, including:a first proximal electrode, mounted on a first shaft of the tool, and / or a second proximal electrode, mounted on the first shaft at a fixed position distally from the first proximal electrode; and / ora distal electrode assembly, including:a first distal electrode, mounted on a second shaft of the tool, and / or a second distal electrode, mounted on the second shaft at a fixed position proximally from the first distal electrode, wherein:the first shaft and the second shaft are telescopically arranged such that second shaft is telescopically extendible distally from the first shaft in a manner that changes an axial distance between the distal electrode assembly and the proximal electrode assembly, and / or the tool is operable to manipulate the distal region between (a) a provisional position in which at least one of the first proximal electrode and the first distal electrode is disposed within the tumor, and (b) a treatment position in which (i) the first proximal electrode and the first distal electrode are both disposed outside of the tumor, and (ii) the second proximal electrode and the second distal electrode are both disposed within the tumor; and / or at the proximal region, a control unit, including bioimpedance-positioning circuitry and electroporation circuitry, and connectable to the proximal region of the tool to electrically connect the control unit to the first and second electrode assemblies, and, while electrically connected to the first and second electrode assemblies, configured to:SNP1010-W001switch between:a positioning mode in which the bioimpedance-positioning circuitry drives an electric current between the first proximal and second proximal electrodes to identify, via detection of bioimpedance between the first proximal electrode and the second proximal electrode, whether the distal region is in the treatment position, and / oran electroporation mode in which the electroporation circuitry, while the distal region is in treatment position, drives an electroporation pulse between (i) the first distal electrode and the second distal electrode, together serving as a distal electroporation electrode, and (ii) the first proximal electrode and the second proximal electrode, together serving as a proximal electroporation electrode.

[0024] In some implementations:the bioimpedance-positioning circuit is a first bioimpedance-positioning circuit, in the positioning mode the system further defines a second bioimpedancepositioning circuit in which the bioimpedance-positioning circuitry drives an electric current between the first distal electrode and the second distal electrode, and / orthe control unit is configured, in the positioning mode, to identify whether the distal region is in the treatment position via (i) measurement of bioimpedance between the first proximal electrode and the second proximal electrode, and (ii) measurement of bioimpedance between the first distal electrode and the second distal electrode.

[0025] In some implementations, the circuitry is configured to switch from the positioning mode into the electroporation mode by placing the first distal electrode in parallel with the second distal electrode, and placing the first proximal electrode in parallel with the second proximal electrode.

[0026] In some implementations, the circuitry is configured to:define the distal electroporation electrode by placing first distal electrode in parallel with the second distal electrode, and / ordefine the proximal electroporation electrode by placing first proximal electrode in parallel with the second proximal electrode.

[0027] There is further provided, in accordance with some implementations, a system for use with a tumor within a subject, the system including:a tool that has:SNP1010-W001an extracorporeal proximal region; and / ora distal region:including a proximal electrode assembly and a distal electrode assembly, and / ormanipulable, from the extracorporeal region, to adjust an interelectrode distance between the proximal electrode assembly and the distal electrode assembly; and / ora control unit, connectable to the proximal region of the tool to electrically connect the control unit to the proximal and distal electrode assemblies, and configured to:receive a start input,receive an interelectrode distance value that is indicative of the interelectrode distance,responsively to the start input, drive a series of electroporation pulses between the proximal electrode assembly and the distal electrode assembly by, for each pulse of the series, applying a respective voltage between the proximal electrode assembly and the distal electrode assembly, and / oriteratively:for a given pulse of the series, measure a current of the pulse between the proximal electrode assembly and the distal electrode assembly, and / or responsively to the current and to the interelectrode distance value, determining a voltage-ceiling, and / orfor a subsequent pulse of the series, increasing the voltage toward the voltage-ceiling.

[0028] In some implementations, the control unit is configured to receive the interelectrode distance responsively to receiving the start input.

[0029] In some implementations, the control unit is configured to determine the interelectrode distance responsively to receiving the start input.

[0030] In some implementations, the control unit is configured to receive the interelectrode distance via manual input.

[0031] In some implementations, the tool includes a linear encoder, and the control unit is configured to receive the interelectrode distance from the linear encoder.SNP1010-W001

[0032] In some implementations, the series of electroporation pulses begins with an initial electroporation pulse whose voltage is an initial voltage, and the control unit is configured to set the initial voltage.

[0033] In some implementations, the control unit is configured to set the initial voltage responsively to a state of the tool.

[0034] In some implementations, the control unit is configured to set the initial voltage responsively to the interelectrode distance.

[0035] There is further provided, in accordance with some implementations, a method for use with a tool that has a distal portion that includes electrodes and that is intracorporeally manipulable to adjust an interelectrode distance between the electrodes, the method including:receiving a start input,receiving an interelectrode distance value that is indicative of the interelectrode distance,responsively to the receiving of the start input, driving a series of electroporation pulses between the electrodes, for each pulse of the series, applying a respective voltage between the electrodes, and / oriteratively:for a given pulse of the series, measuring a current of the pulse between the electrodes, and / orresponsively to the current and to the interelectrode distance value, determining a voltage-ceiling, and / orfor a subsequent pulse of the series, increasing the voltage toward the voltageceiling.

[0036] In some implementations, measuring a current of the pulse between the electrodes is done manually.

[0037] In some implementations, measuring a current of the pulse between the electrodes is done electromechanically.

[0038] In some implementations, determining a voltage-ceiling is done manually.

[0039] In some implementations, determining a voltage-ceiling is done electromechanically.SNP1010-W001

[0040] In some implementations, increasing the voltage toward the voltage-ceiling is done manually.

[0041] In some implementations, increasing the voltage toward the voltage-ceiling is done electromechanically.

[0042] There is further provided, in accordance with some implementations, a method for use with a tool that has a proximal portion that includes a control unit, and has a distal portion that includes electrodes, the method including:advancing electrodes to a provisional position within a subject,manipulating electrodes into a treatment position, such that the electrodes will be distant from each other,providing the control unit with an electrode distance input, and / orproviding the control unit with a start input such that the control unit:drives a series of electroporation pulses between the electrodes by, for each pulse of the series, applying a respective voltage between the electrodes, and / or iteratively:for a given pulse of the series, measure a current of the pulse between the electrodes, and / orresponsively to the current and to an interelectrode distance value, determine a voltage-ceiling, and / orfor a subsequent pulse of the series, increase the voltage toward the voltage-ceiling.

[0043] In some implementations, advancing of the electrodes is done by an endoscope.

[0044] In some implementations, the provisional position is in the vicinity of a tumor.

[0045] In some implementations, the treatment position is inside a tumor.

[0046] In some implementations, the distance between the electrodes is a coaxial distance.

[0047] In some implementations, the distance between the electrodes is a parallel distance.

[0048] In some implementations, providing the control unit with the electrode distance input is done manually.

[0049] In some implementations, providing the control unit with the electrode distance input is done electromechanically.SNP1010-W001

[0050] In some implementations, providing the control unit with a start input is done manually.

[0051] In some implementations, providing the control unit with a start input is done electromechanically.

[0052] There is further provided, in accordance with some implementations, a system for use with a tumor within a subject, the system including a tool that includes:a sheath assembly, including:a flexible sheath, having a distal part that includes a sheath opening, a sheath stock, fixed to a proximal part of the sheath, and configured to transbronchially advance the distal part of the sheath into an airway of the subject; a first manipulator assembly, including:a first shaft, disposed coaxially within the sheath;at a distal part of the first shaft, a proximal electrode assembly, including:a first proximal electrode, and / ora second proximal electrode, mounted at a fixed position distally from the first proximal electrode; and / ora first-manipulator stock, fixed to a proximal part of the first shaft, and configured to, by sliding the first shaft distally through the sheath, advance the proximal electrode assembly out of the sheath opening and through a wall of the airway toward the tumor;a second manipulator assembly, including:a second shaft, disposed coaxially within the first shaft;at a distal part of the second shaft, a distal electrode assembly, including: a first distal electrode, and / ora second distal electrode, mounted at a fixed position proximally from the first distal electrode; and / ora second-manipulator stock, fixed to a proximal part of the second shaft, and configured to, by sliding the second shaft distally through the first shaft, advance the distal electrode assembly distally out of the first shaft and through the tumor; a first fastener, at a proximal part of the tool, the first fastener being manipulable between:an unlocked state, and / orSNP1010-W001a locked state that inhibits sliding of the first shaft through the sheath by fastening the first-manipulator stock to the sheath stock; and / ora second fastener, at a proximal part of the tool, the second fastener being manipulable between:an unlocked state, and / ora locked state that inhibits sliding of the second shaft through the first shaft by fastening the second-manipulator stock to the first-manipulator stock.

[0053] In some implementations, the system is for use with an endoscope, and the sheath is configured to be advanced through the endoscope such that a distal opening of the sheath becomes exposed out of the endoscope.

[0054] In some implementations, the first shaft of the first manipulator assembly includes an unsupported extension configured to limit compressive forces on the first shaft.

[0055] In some implementations, the first shaft of the first manipulator assembly includes an unsupported extension configured to absorb shocks acting upon the first shaft.

[0056] In some implementations, the second shaft of the second manipulator assembly includes an unsupported extension configured to limit compressive forces on the second shaft.

[0057] In some implementations, the second shaft of the second manipulator assembly includes an unsupported extension configured to absorb shocks acting upon the second shaft.

[0058] In some implementations, the sheath stock is distal to the second-manipulator stock.

[0059] In some implementations, the tool includes a gauge indicating an axial position of the first-manipulator stock relative to the sheath stock.

[0060] In some implementations, the tool includes a gauge indicating an axial position of the second-manipulator stock relative to the first-manipulator stock.

[0061] In some implementations, an axial position of the first-manipulator stock relative to the sheath stock is manually adjustable.

[0062] In some implementations, an axial position of the first-manipulator stock relative to the sheath stock is electromechanically adjustable.

[0063] In some implementations, an axial position of the first-manipulator stock relative to the second-manipulator stock is manually adjustable.SNP1010-W001

[0064] In some implementations, an axial position of the first-manipulator stock relative to the second-manipulator stock is electromechanically adjustable.

[0065] In some implementations, the first fastener includes a set-screw mounted on the sheath stock, and manipulable to the locked state by screwing into contact with the first-manipulator stock.

[0066] In some implementations, the second fastener includes a set-screw mounted on the second-manipulator stock, and manipulable to the locked state by screwing into contact with the first-manipulator stock.

[0067] In some implementations, the first fastener includes a pin mounted on the sheath stock, and manipulable to the locked state by pushing into a pinhole defined in the first-manipulator stock.

[0068] In some implementations, the second fastener includes a pin mounted on the second-manipulator stock, and manipulable to the locked state by pushing into a pinhole defined in the first-manipulator stock.

[0069] In some implementations, the first fastener is manually manipulable.

[0070] In some implementations, the second fastener is manually manipulable.

[0071] In some implementations, the first fastener is electromechanically manipulable.

[0072] In some implementations, the second fastener is electromechanically manipulable.

[0073] In some implementations, the second proximal electrode is shaped to define a hollow needle.

[0074] In some implementations, the first-manipulator stock is slidable into the sheath stock and slidable into the second-manipulator stock.

[0075] In some implementations, the first-manipulator stock is:slidable distally into the sheath stock to slide the first shaft distally through the sheath, and / orslidable proximally into the second-manipulator stock to slide the second shaft distally through the first shaft.

[0076] In some implementations, an axial position of the first stock relative to the second stock is adjustable manually.SNP1010-W001

[0077] In some implementations, an axial position of the first stock relative to the second stock is adjustable electromechanically.

[0078] There is further provided, in accordance with some implementations, a system for use with a tumor within a subject, the system including:a tool that has an extracorporeal proximal region and a distal region, and that includes, at the distal region:an electrode assembly, including:a first electrode, mounted on a shaft of the tool, and / ora second electrode, mounted on the shaft at a fixed position distally from the first electrode; wherein:the tool is operable to manipulate the distal region into a treatment position in which (i) the first electrode is disposed outside of the tumor, and (ii) the second electrode is disposed within the tumor; and / ora control unit, connectable to the proximal region of the tool to electrically connect the control unit to the electrode assembly, and, while electrically connected to the electrode assembly, configured to:switch between:a positioning mode in which the system defines a positioning circuit in which the first electrode and the second electrode are in series with each other, and / oran electroporation mode in which the system defines an electroporation circuit in which the first electrode and the second electrode are in parallel with each other to collectively define an electroporation electrode,in the positioning mode, identify, via measurement of bioimpedance between the first electrode and the second electrode, whether the distal region is in the treatment position, and / orwhile the distal region is in the treatment position, drive the electroporation electrode to apply an electroporation pulse.

[0079] In some implementations:the electrode assembly is a first electrode assembly,the tool includes, at the distal region, a second electrode assembly, and / orSNP1010-W001the control unit is configured to apply the electroporation pulse between the electroporation electrode and the second electrode assembly.

[0080] In some implementations, the second electrode assembly includes exactly one electrode, and the control unit is configured to apply the electroporation pulse between the electroporation electrode of the first electrode assembly and the exactly one electrode of the second electrode assembly.

[0081] In some implementations:the second electrode assembly includes a first second-assembly electrode and a second second-assembly electrode, and / orthe control unit is configured:to place the first second-assembly electrode and the second second-assembly electrode in series with each other upon switching to the positioning mode, and / or to place the first second-assembly electrode and the second second-assembly electrode in parallel with each other upon switching to the electroporation mode.

[0082] In some implementations, the second electrode assembly is proximal to the first electrode assembly.

[0083] In some implementations, the second electrode assembly is distal to the first electrode assembly.

[0084] In some implementations, the second electrode assembly is mounted at a fixed axial distance from the first electrode assembly.

[0085] In some implementations, the tool is configured to facilitate adjustment of an axial distance between the first electrode assembly and the second electrode assembly.

[0086] In some implementations:the system is for use with a skin-patch electrode, and / orthe control unit is configured to apply the electroporation pulse between the electroporation electrode and the skin-patch electrode.

[0087] The present invention will be more fully understood from the following detailed description of applications thereof, taken together with the drawings, in which:SNP1010-W001BRIEF DESCRIPTION OF THE DRAWINGS

[0088] Figs. 1A-B are schematic illustrations of a system, in accordance with some implementations;

[0089] Figs. 2, 3, 4A-B, 5A-B, 6A-B, and 7A-B are schematic illustrations of a tool of the system, in accordance with some implementations;

[0090] Figs. 8A-G and 9 are schematic illustrations of, and a flowchart relating to, a technique for use with the system, in accordance with some implementations;

[0091] Figs. 10-14 are schematic diagrams illustrating processes that may be performed with the system, such as by a control unit of the system, in accordance with some implementations; and

[0092] Figs. 15A-G are schematic illustrations of a tool of the system, in accordance with some implementations.DETAILED DESCRIPTION OF IMPLEMENTATIONS

[0093] The present disclosure includes different variants of some elements. Variants of a given element typically have the same structure and / or function as each other except for any differences described. For any given element for which different variants are disclosed, the identical name is used for each variant, in order to denote that they are, in fact, variants of the same given element. Unless stated otherwise, applications of the devices, systems, and techniques described herein may include any arrangement in which one variant of an element is substituted with another identically-named variant of that element. Furthermore, throughout the figures, suffixes are used to denote different variants of the same element. Unless stated otherwise, such variants may be substituted with each other, mutatis mutandis. That is, unless stated otherwise, any element having a given reference numeral may be substituted with any other element (i.e. any other variant of the element) having the same reference numeral, independent of any suffix.

[0094] In order to avoid undue clutter from having too many reference numbers and lead lines on a particular drawing, some elements are introduced via one or more drawings and not explicitly identified in every other drawing that contains that element.

[0095] Reference is made to Figs. 1A-B, 2, 3, 4A-B, 5A-B, 6A-B, 7A-B, 8A-G, 9, 10, 11, 12, 13, 14 and 15A-G which are schematic illustrations and flowcharts relating to a systemSNP1010-W00120, and processes and techniques for use therewith, in accordance with some implementations.

[0096] System 20 is described herein in the context of treating a tumor 4 in a lung 12 of a subject. System 20 may be particularly suited to such a tumor due to the bioimpedance of lung tumors typically being substantially lower than that of the surrounding tissue - e.g. due to the lung parenchyma having particularly high bioimpedance. However, it is to be understood that the scope of the present disclosure includes the use of system 20, its components, and / or techniques described herein, mutatis mutandis, to treat other lesions, including in other tissues in which the lesion's bioimpedance is substantially different than that of its surrounding tissues, and or in which the boundary of the lesion is unfavorable to propagation of electroporation pulses into the surrounding tissue.

[0097] In some implementations, and as shown in Fig. 1, system 20 includes a tool 100, and / or a control unit 500, which is electrically connectable to the tool - e.g. to a proximal region 102 thereof. In some implementations, tool 100 is electrically connectable to control unit 500 via one or more cords 561 and / or 562. For example, tool 100 (e.g. proximal region 102 thereof) can comprise a connector 460 (e.g. a jack, a socket, etc.) via which the electrical connection can be made. Connector 460 may comprise multiple electrical terminals via which the electrical connection can be made.

[0098] Control unit 500 may comprise one or more data-processing systems (DPSs) that perform, or facilitate performance of, functions of the control unit described herein. The data-processing system may be, or may be a component of, a discrete (e.g. purpose-made) device. For some applications, the data-processing system is a general -purpose data-processing system (e.g. a processor of a general -purpose computer) programmed to run a program.

[0099] In the present disclosure, the term data-processing system (DPS) may refer to, be part of, or include an Application Specific Integrated Circuit (ASIC); a digital, analog, or mixed analog / digital discrete circuit; a digital, analog, or mixed analog / digital integrated circuit; a combinational logic circuit; a field programmable gate array (FPGA); a processor (shared, dedicated, group) that executes code; memory (shared, dedicated, or group) that stores code executed by a processor; other suitable hardware components, such as optical, magnetic, or solid state drives, that provide the described functionality; or a combination of some or all of the above, such as in a system-on-chip. The term code, as used above, may include software, firmware, and / or microcode, and may refer to programs, routines, algorithms,SNP1010-W001functions, classes, and / or objects. The term shared processor encompasses a single processor that executes some or all code from multiple modules. The term group processor encompasses a processor that, in combination with additional circuitry (e.g. processors), executes some or all code from one or more modules. The term shared memory encompasses a single memory that stores some or all code from multiple modules. The term group memory encompasses a memory that, in combination with additional memories, stores some or all code from one or more modules. The term memory may be subset of the term computer-readable medium. The term computer-readable medium does not encompass transitory electrical and electromagnetic signals propagating through a medium, and may therefore be considered tangible and non-transitory. Non-limiting examples of a non-transitory tangible computer readable medium include nonvolatile memory, volatile memory, magnetic storage, and optical storage.

[0100] In some implementations, and as shown, tool 100 has a handle assembly 110 at proximal region 102, and one or more electrode assemblies at a distal region 104 of the tool.

[0101] In some implementations, tool 100 may be considered to comprise three discrete assemblies: a sheath assembly 200, a first manipulator assembly 300, and a second manipulator assembly 400. Fig. 1A shows system 20 overall (i.e., in an assembled state of the system), and Fig. IB is a cross-section at a respective axial location along distal region 104 while the system is in the assembled state. Fig. 2 shows these assemblies completely separated from each other, alongside each other, and Fig. 3 shows these assemblies partly separated from each other, colinear with each other. Figs. 4A-B show, in perspective and cross-section view respectively, more details of sheath assembly 200. Figs. 5A-B show, in perspective and cross-section view respectively, more details of first manipulator assembly 300. Figs. 6A-B show, in perspective and cross-section view respectively, more details of second manipulator assembly 400. Fig. 7A-B are side and section views, respectively, of tool 100.

[0102] Sheath assembly 200 may include a flexible sheath 220, and a sheath stock 230 (e.g. a handle) that is fixed to a proximal part of the sheath. At a distal part (e.g. distal end) of sheath 220, the sheath defines a sheath opening 222. The distal part of sheath 220 is transluminally advanceable through the body via an endoscope, such as transbronchially into an airway of a subject. In some implementations, sheath assembly 200 may include a screw thread 250 to facilitate attachment to another medical device (e.g. an endoscope). As shown (e.g. in Figs. 4A-B) thread 250 may be distally-facing and / or disposed at a distal end ofSNP1010-W001sheath stock 230 - e.g. in the vicinity of the point at which the sheath stock is attached to sheath 220.

[0103] First manipulator assembly 300 may include a flexible first shaft 320, and a first-manipulator stock 330 that is fixed to a proximal part of the first shaft. At a distal part of shaft 320, assembly 300 comprises an electrode assembly 310 which, due to the construction of tool 100, is referred to herein as a proximal electrode assembly.

[0104] Proximal electrode assembly 310 may include a first proximal electrode 312, mounted on shaft 320, and a second proximal electrode 314, mounted on shaft 320 at a fixed position distally from the first proximal electrode. Electrodes 314 and 312 may be separated (e.g. axially) by an insulator 311, which may be annular and / or may circumscribe shaft 320. In some implementations, and as shown, second proximal electrode 314 is shaped to define a hollow needle tip 316.

[0105] Second manipulator assembly 400 may include a flexible second shaft 420, and a second-manipulator stock 430 (e.g. a handle) that is fixed to a proximal part of the second shaft. At a distal part of shaft 420, assembly 400 comprises an electrode assembly 410 which, due to the construction of tool 100, is referred to herein as a distal electrode assembly. Distal electrode assembly 410 includes a first distal electrode 412, mounted on shaft 420, and a second distal electrode 414, mounted on shaft 420 at a fixed position proximally from the first distal electrode. Electrodes 414 and 412 may be separated (e.g. axially) by an insulator 411, which may be annular and / or may circumscribe shaft 420.

[0106] In the example shown, connector 460 is shown at a proximal end of second manipulator assembly 400 (e.g. mounted on stock 430 thereof), however, it is to be understood that the electrical connection of tool 100 to control unit 500 could be established in any other way, e.g., via individual connections between assemblies 300 and 400 respectively.

[0107] Once tool 100 has been assembled, first shaft 320 is disposed coaxially within sheath 220 and second shaft 420 is disposed coaxially within first shaft 320. In some implementations, and as shown, once assembled, sheath stock 230 is distal to first-manipulator stock 330, which, in turn, is distal to second-manipulator stock 430. In some implementations first shaft 320 can extend through first-manipulator stock 330 and proximally out of a proximal end of the stock 330, e.g., such that the first shaft extends into stock 430 in the assembled state of tool 100.SNP1010-W001

[0108] Fig. IB shows a cross section IB at a location along sheath 220. Sheath 220 is the outer tube in the section. First shaft 320 constitutes the next tube within the cross section. As shown, shaft 320 may have more than one layer - e.g. an outer layer 320' and an inner layer 320" between which wires 317 and 318 are disposed (e.g. sandwiched). The wires provide electrical connection between connector 460 and electrode assembly 310 (e.g. for electroporation pulses, bioimpedance signals, etc.). The next tube in cross section IB is second shaft 420 - e.g. the innermost tube. Shaft 420 may have more than one layer - e.g. a tube 418 and a wire 413 which is disposed within tube 418. Both tube 418 and wire 413 may provide electrical connection between connector 460 electrode assembly 410 (e.g. for electroporation pulses, bioimpedance signals, etc.). For example, wire 413 may provide the electrical connection to electrode 412, and tube 418 (which may itself be metallic) may provide the electrical connection to electrode 414. As shown, wire 413 may be coated in order to electrically insulate it from tube 418. Shaft 420 may include an insulating layer 419 that electrically insulates it (e.g. tube 418 thereof) - e.g. from shaft 320.

[0109] In some implementations, and as illustrated in Figs. 7A-B, in an assembled state of tool 100, a distal part of first-manipulator stock 330 is disposed within sheath stock 230 (e.g. within a cavity 238 defined in the sheath stock), and a proximal part of the first-manipulator stock is disposed within second-manipulator stock 430 (e.g. within a cavity 438 defined in the second-manipulator stock), such that sheath stock 230 and / or second-manipulator stock 430 are slidable over first-manipulator stock 330. That is, in such implementations, first-manipulator stock 330 is slidable into sheath stock 230 and slidable into second-manipulator stock 430.

[0110] Tool 100 may be configured such that sliding of first-manipulator stock 330 distally within (e.g., further into) sheath stock 230 slides first shaft 320 distally through sheath 220.[OHl] Tool 100 may be configured such that sliding of first-manipulator stock 330 proximally within (e.g., further into) second-manipulator stock 430 slides first shaft 320 proximally with respect to second shaft 420 (e.g., such that a distal end of shaft 420 becomes progressively exposed out of first shaft 320).

[0112] As described in more detail hereinbelow, tool 100 (e.g. handle assembly 110 thereof) may comprise one or more fasteners 240 and 440 that inhibit sliding between the stocks of the handle assembly. These fasteners may also maintain coupling between the stocks. In the example shown, these fasteners comprise set screws (which may be referred to as 240 and 440), but it is to be understood that the scope of the invention includes the use of otherSNP1010-W001fasteners, mutatis mutandis. Fasteners 240 and / or 440 can be manually manipulatable (e.g., by a user rotating or pushing the screws), or manipulatable via electronic means (e.g., via control unit 500). In some such implementations, fasteners 240 and 440 can be electromechanically manipulable.

[0113] In some implementations, sheath assembly 200 is reversibly fastenable to first manipulator assembly 300 via fastener 240, which is manipulable between (i) an unlocked state, and (ii) a locked state that inhibits sliding of shaft 320 through sheath 220 by fastening sheath stock 230 to first-manipulator stock 330. Similarly, second manipulator assembly 400 may be fastened to first manipulator assembly 300 via fastener 440, which is manipulable between (i) an unlocked state, and (ii) a locked state that inhibits sliding of shaft 420 through shaft 320 by fastening second-manipulator stock 430 to first-manipulator stock 330.

[0114] In the example shown, each of fasteners 240 and 440 are embodied by a set-screw that extends through stocks 230 and 430 respectively to contact a fricative surface 340 of first-manipulator stock 330 - e.g. such that friction inhibits sliding between the stocks. However, it is to be understood that other types of fasteners may be used.

[0115] For example, in some implementations (not shown in the figures), any of fasteners 240 and / or 440 can be embodied by a pin that is coupled to, or extends through, its respective stock (i.e., stocks 230 and 430 respectively), the pin being manipulable into its locked state by being pushed into a respective pinhole defined by first-manipulator stock 330. Alternatively or additionally, fastener 240 and / or fastener 440 may comprise a clip, a clamp, or other suitable means for inhibiting sliding between the stocks.

[0116] In some implementations, tool 100 includes a first gauge 331 indicating an axial position of the first-manipulator stock relative to the sheath stock.

[0117] In some implementations, tool 100 includes a second gauge 333 indicating an axial position of the second-manipulator stock relative to the first-manipulator stock.

[0118] In some implementations, and as shown in Fig. 7A, each of the first and second gauges may comprise a scale (332 and 334, respectively) that is defined by first-manipulator stock 330. In some implementations, each scale 332 and 334 is engraved or printed on stock 330. In order to indicate to the user (e.g., physician) the relative position of a distal end of first shaft 320 with respect to sheath opening 222, sheath stock 230 can define a window 232, positioned axially along scale 332, the axial position of the window with respect to the scale thereby indicating the relative position of the distal end of shaft 320 with respect toSNP1010-W001sheath 220 within the tissue (e.g., the extent that the distal end of the first shaft is exposed out of the sheath). Similarly, in order to indicate to the user (e.g., physician) the relative position of a distal end of second shaft 420 with respect to a distal end of first shaft 320, second stock 430 can define a window 432, that is positioned axially along scale 334, the axial position of the window with respect to the scale thereby indicating the relative position of the distal end of shaft 420 with respect to shaft 320 within the tissue (e.g., the extent that the distal end of the second shaft is exposed out of the first shaft). In some implementations, the axial position of first-manipulator stock 330 relative to the positions of sheath stock 230 and / or second-manipulator stock 430 may be adjusted manually - e.g. by unlocking the respective fastener, pushing or pulling the stocks, and then refastening the fastener.

[0119] In some implementations, the first and / or second gauges may be electronic gauges -e.g. linear encoders.

[0120] In some implementations, the axial position of the first-manipulator stock 330 relative to the positions of sheath stock 230 and / or second-manipulator stock 430 may be adjusted electromechanically - e.g. directed by control unit 500.

[0121] In some implementations, in at least some states of tool 100, a segment 322 of first shaft 320 extends unsupported within cavity 238 - e.g. between a distal end of stock 330 and a proximal end of sheath 220. In some implementations, this unsupported segment 322 of first shaft 320 may serve as a shock-absorber. In some implementations, during use of tool 100, this unsupported segment 322 may protect against excessive forces and / or speeds applied to first shaft 320 - e.g. by buckling (e.g., compressing and / or collapsing) in response to forces that exceed a pre-defined threshold magnitude. Thus, unsupported segment 322 may serve as a sacrificial component to protect the subject being treated. For example, segment 322 may buckle responsively to first shaft 320 being pushed distally with too greater force and / or speed, thus preventing sharpened distal tip 316 from inadvertently damaging tissue distal to itself.

[0122] Similarly, in some implementations, in at least some states of tool 100, a segment 422 of second shaft 420 extends through cavity 438 unsupported - e.g. until it enters first shaft 320. In some implementations, this unsupported segment 422 of second shaft 420 may serve as a shock-absorber. In some implementations, and as explained hereinabove with respect to segment 322, this unsupported segment 422 may protect against pushing shaft 420 with excessively force and / or speed - e.g. by buckling in response to compressive force thatSNP1010-W001exceeds than a pre-defined threshold magnitude. Thus, unsupported segment 422 may serve as a sacrificial component to protect the subject being treated.

[0123] Reference is now made to Figs. 8A-G, which are schematic illustrations showing some steps of an example technique in which system 20 is used to treat a subject 10, in accordance with some implementations.

[0124] In the example shown, an endoscope 30 is used to facilitate advancement and / or positioning of tool 100. However, it is to be noted that, in some implementations, tool 100 may be advanced directly through the anatomy.

[0125] A distal end of endoscope 30 is advanced transbronchially to an airway 14 of a lung 12 of a subject (Fig. 8A). Tool 100 is then advanced transbronchially through endoscope 30 - e.g. until handle assembly 110 reaches a proximal part of the endoscope (Fig. 8B). Tool 100 may then be secured to the endoscope by screwing thread 250 into a corresponding thread of the endoscope.

[0126] Alternatively, endoscope 30 may be advanced with tool 100 already disposed within it.

[0127] The advancement of tool 100 may be performed while the tool is in a delivery configuration in which shafts 320 and 420 are disposed within sheath 220 - e.g., such that the distal ends of shafts 320 and 420 are disposed within the sheath and do not extend out of sheath opening 222. Tool 100 can be retained in this delivery state by fasteners 240 and 440 being in their locked states. In the example shown, this configuration is represented by gauges 331 and 333 both indicating zero - i.e., that there is no exposure of the distal end of first shaft out of sheath opening 222 (as shown by gauge 331), and there is no exposure of second shaft 420 out of first shaft 320 (as shown by gauge 333).

[0128] Fig. 8C illustrates sheath opening 222 disposed outside of endoscope 30 within airway 14 - e.g. a different representation / view of the state shown in Fig. 8B. In some implementations, at this stage, sheath opening 222 is positioned against a wall of airway 14, e.g., in preparation for the subsequent puncture of the airway via tool 100.

[0129] Once it has been determined that sheath 220 is appropriately positioned, proximal electrode assembly 310 is advanced toward, and typically into, a tumor 4, using needle tip 316 to penetrate the tissue (Fig. 8D). In the example shown, needle tip 316 has punctured through a wall 16 of airway 14, penetrating the lung parenchyma and the tumor.SNP1010-W001

[0130] In the example shown, distal electrode assembly 410 is advanced simultaneously with proximal electrode assembly 310, while the distal electrode assembly remains within shaft 320. This may be achieved, for example, by pushing both first-manipulator stock 330 and second-manipulator stock 430 together distally in relation to sheath stock 230. Such pushing may be achieved by pushing second-manipulator stock 430 distally while fastener 240 is unlocked and fastener 440 remains locked, such that stock 430 moves toward stock 230, and stock 330 slides into stock 230. In this example, the resulting configuration is represented by gauge 331 indicating 2 (i.e. shaft 320 has moved distally with respect to sheath 220) while gauge 333 continues to indicate zero (i.e. shaft 420 has not moved with respect to shaft 320).

[0131] Distal electrode assembly 410, on shaft 420, may then be exposed out of the distal end of shaft 320 (Fig. 8E). In the example shown, this exposure involves pushing shaft 420 distally within tumor 4. However, it is to be understood that, depending on the prior position of shaft 320, the exposure may involve retracting shaft 320 with respect to the tumor - e.g. while shaft 420 remains stationary. For example, the figures show shaft 320 (e.g. needle tip 316 thereof) used to penetrate partway through tumor 4 (e.g. piercing a proximal boundary of the tumor), and shaft 420 being subsequently advanced distally to penetrate the remainder of the tumor. However, it is to be understood that other approaches are possible. For example, shaft 320 (e.g. needle tip 316 thereof) may be advanced all the way through the tumor (e.g. piercing the proximal boundary and a distal boundary of the tumor), and then retracted leaving shaft 420 in place.

[0132] Such exposure of assembly 410 may be achieved by bringing stocks 230 and 430 closer to each other (e.g. by pushing stock 430 toward stock 230) while fastener 440 is unlocked and fastener 240 is locked, such that stock 430 slides over stock 330 (e.g., such that stock 330 becomes positioned deeper within cavity 438). In this example, the resulting configuration is represented by gauge 333 now indicating 2 (i.e. shaft 420 has moved distally with respect to shaft 320) while gauge 331 continues to indicate 2 (i.e. shaft 320 has not moved with respect to sheath 220).

[0133] Once proximal electrode assembly 310 is exposed from sheath 220 and distal electrode assembly 410 is exposed from shaft 320, distal region 104 may be, or may be considered to be, in a provisional position with respect to tumor 4.SNP1010-W001

[0134] System 20 may then be used to manipulate distal region 104 into a treatment position for electroporation treatment of tumor 4 (Fig. 8F). Techniques for such manipulation are described hereinbelow.

[0135] As shown in Fig. 8F, in the treatment position, electrodes 312 and 412 (e.g. in their entirety) are both disposed outside of the tumor, and electrodes 314 and 414 (e.g. in their entirety) are both disposed within the tumor. In some implementations, in the treatment position, insulators 311 and 411 lie on (e.g. straddle) respective boundaries of the tumor. The provisional position from which distal region 104 is manipulated into the treatment position may be less well defined - e.g. it may simply be the position in which the distal portion is initially disposed. For example, the provisional position may be a position in which electrode 312 and / or 412 is also disposed within tumor 4. Alternatively or additionally, the provisional position may be a position in which electrode 314 and / or 414 is at least partially (e.g. entirely) disposed outside of tumor 4 (e.g. as shown in Fig. 8E).

[0136] To achieve having electrodes 312 and 412 (e.g. in their entirety) both disposed outside of the tumor and electrodes 314 and 414 (e.g. in their entirety) both disposed within the tumor, the tumor boundaries may be electronically sensed by measuring bioimpedance between electrodes, as described hereinbelow.

[0137] After positioning proximal electrode assembly 310 and distal electrode assembly 410 (i.e. once distal region 104 is in the treatment position), electroporation may take place (Fig.8G). During electroporation, control unit 500 may drive a series of electroporation pulses by applying a respective voltage between the proximal electrode assembly and the distal electrode assembly.

[0138] Fig. 9 shows a flow chart 600 summarizing at least some steps of the aforementioned techniques, in accordance with some implementations. Step 610 includes advancing a needle-tipped shaft, such as first shaft 320, through an airway wall and into a tumor. Step 620 includes advancing an inner shaft (e.g. second shaft 420) out of the needle-tipped shaft. Step 630 includes positioning electrode assemblies (e.g. electrode assemblies 310 and 410) in a treatment position at tumor boundaries such that a first proximal and distal electrodes (e.g. electrodes 312 and 412 respectfully) are outside of the tumor and second proximal and distal electrodes (e.g. electrodes 314 and 414 respectfully) are inside the tumor. Step 640 includes electroporating the tumor.SNP1010-W001

[0139] In some implementations, the techniques described herein may be controlled by control unit 500 which, as described hereinabove, may be connectable to a proximal region of tool 100 to electrically connect the control unit to proximal electrode assembly 310 and distal electrode assembly 410.

[0140] In some implementations, control unit 500 is configured, while electrically connected to the first and second electrode assemblies, to switch between (i) a positioning mode and (ii) an electroporation mode. In some implementations, this switching is performed by / upon human input. In some implementations, this switching is performed automatically. In some implementations, this switching is performed as little as once per procedure - e.g. beginning in the positioning mode until the electrodes are appropriately positioned, and then switching into the electroporation mode. In some implementations, this switching is performed multiple times - e.g. for re-verifying electrode positioning and / or adjusting it according to progress of the procedure.

[0141] In some implementations, while in the positioning mode, system 20 defines a positioning circuit 510 in which first and second proximal electrodes 312 and 314 are in series with each other, and first and second distal electrodes 412 and 414 are in series with each other. This is schematically illustrated in Fig. 10 (left side). Control unit 500 includes positioning circuitry that can be included in the positioning circuit.

[0142] In some implementations, while in the electroporation mode, system 20 defines an electroporation circuit 520 in which (i) first distal electrode 412 and second distal electrode 414 are in parallel with each other - e.g. collectively defining a distal electroporation electrode, and (ii) first proximal electrode 312 and second proximal electrode 314 are in parallel with each other - e.g. collectively defining a proximal electroporation electrode that is in series with the distal electroporation electrode. This is schematically illustrated in Fig.10 (right side). Control unit 500 includes electroporation circuitry that can be included in the electroporation circuit.

[0143] In some implementations, in the electroporation mode, second distal electrode 414 alone serves as the distal electroporation electrode. In some implementations, in the electroporation mode, second proximal electrode 314 alone serves as the proximal electroporation electrode. For example, an electroporation voltage may be applied between electrodes 314 and 414. Therefore, in some implementations, in the electroporation mode, electrodes 412 and 414 are not in parallel with each other, and / or electrodes 312 and 314 are not in parallel with each other.SNP1010-W001

[0144] Alternatively or additionally, while in the electroporation mode, an electroporation voltage may be applied between first and second distal electrodes 412 and 414 and / or between first and second proximal electrodes 312 and 314. Thus, electroporation may be carried out in more than one location in the tumor at the same time.

[0145] In some implementations, while in the positioning mode, control unit 500 may identify, via bioimpedance signals received from electrode 412 and / or electrode 312, whether the distal region is in the treatment position. For example, bioimpedance between electrodes 412 and 414 may be determined by applying a voltage between these electrodes.

[0146] In some implementations, while in positioning mode, the bioimpedance-positioning circuitry may drive an electric voltage between first proximal electrode 312 and second proximal electrode 314 to identify, via detection of bioimpedance between first proximal electrode 312 and second proximal electrode 314, whether proximal electrode assembly 310 is in the treatment position; and the bioimpedance-positioning circuitry may drive an electric voltage between first distal electrode 412 and second distal electrode 414 to identify, via detection of bioimpedance between first distal electrode 412 and second distal electrode 414, whether distal electrode assembly 410 is in the treatment position. Thus, the tumor boundaries may be electronically sensed by first and second proximal electrodes 312 and 314 and by first and second distal electrodes 412 and 414.

[0147] In some other examples, positioning may be achieved via measurement of bioimpedance between electrodes 412 and 312.

[0148] In some implementations, distal region 104 is considered to be in the treatment position when (i) electrodes 312 and 412 (e.g. in their entirety) are both disposed outside of the tumor, and (ii) electrodes 314 and 414 (e.g. in their entirety) are both disposed within the tumor.

[0149] In some implementations, the circuitry is configured to switch from the positioning mode into the electroporation mode by placing the first distal electrode 412 in parallel with second distal electrode 414, and by placing first proximal electrode 312 in parallel with second proximal electrode 314. In this context, the meaning of "in parallel" is in accordance with electronics terminology - i.e. having the same voltage applied thereto.

[0150] In some implementations, the circuitry is configured to (i) define the distal electroporation electrode by placing first distal electrode 412 in parallel with second distalSNP1010-W001electrode 414, and (ii) define the proximal electroporation electrode by placing first proximal electrode 312 in parallel with second proximal electrode 314.

[0151] In some implementations, while the distal region is in the treatment position, and while the circuitry is in the electroporation mode, the electroporation circuitry may drive an electroporation pulse between (i) first distal electrode 412 and second distal electrode 414, together serving as a distal electroporation electrode, and (ii) first proximal electrode 312 and second proximal electrode 314, together serving as a proximal electroporation electrode.

[0152] In some implementations, while in the electroporation mode and while the distal region is in the treatment position, the electroporation circuitry drives an electroporation pulse between the proximal electroporation electrode and the distal electroporation electrode.

[0153] Fig. 11 is a flow chart showing at least some steps of a technique or procedure 700 that may be used with the electroporation described hereinabove - e.g. for the application of electroporation pulses. This technique may be performed by control unit 500. For example, this technique may be performed automatically by control unit 500 each time that the control unit performs electroporation.

[0154] The technique described with reference to Fig. 11 may allow the use of electroporation pulses having a voltage of sufficient magnitude to treat a tumor, while avoiding electrical arcing due to excessively high voltage. Such arcing might otherwise cause harm to surrounding tissues and introduce unpredictability into the treatment.

[0155] The propagation of an electroporation pulse through tissue can differ on a case-by-case basis (e.g. between tumors, between individuals), and can also be dependent on the distance between the electrodes between which the pulse is driven (the "interelectrode distance"). Therefore, it may be challenging to find a particular voltage that can be successfully used for tumor electroporation in various tissue structures of many individuals without risking unsuccessful electroporation in some instances (e.g. due to the voltage being too low for those particular instances) and undesirable arcing in other instances (e.g. due to the voltage being too high for those particular instances). Furthermore, as the electroporation process progresses, tissue changes may alter the voltage at which arcing will occur - the "arcing threshold".

[0156] It is to be noted that the term "interelectrode distance" (including in the specification and the claims) means the distance between the two closest parts of the electrodes (or pairsSNP1010-W001of electrodes) between which the electroporation pulse is driven. So, for example, in system 500, irrespective of whether the electroporation pulse is driven (a) between electrode 314 and electrode 414, or (b) between electrodes 312 and 314 and electrodes 412 and 414, the interelectrode distance is the distance between the distal end of electrode 314 and the proximal end of electrode 414.

[0157] The present technique involves beginning the electroporation process at an initial voltage that is reliably below the arcing threshold, and ramping up the voltage for subsequent pulses, while monitoring the resulting current of the pulses in order to identify when the voltage is approaching the arcing threshold. For example, control unit 500 may monitor the voltage: current ratio for a given pulse, and / or the ratio between (i) the difference in voltage between pulses, and (ii) the difference in current between those pulses. That is, control unit 500 may determine a voltage-ceiling for electroporation pulses and, for subsequent pulses, progressively increase the voltage toward the voltage-ceiling (e.g. without exceeding the ceiling). The determination of the voltage-ceiling may also take into account the interelectrode distance.

[0158] In some implementations, control unit 500 determines the voltage-ceiling dynamically along the entire electroporation process.

[0159] In some implementations, the initial voltage is selected (e.g. automatically by control unit 500) responsively to the interelectrode distance and / or to a state of the tool (e.g. "ready", "positioned" and / or "start button was pushed" states).

[0160] In some implementations, the electroporation process begins responsively to a start input 720 - e.g. pushing a "start" button on control unit 500.

[0161] In some implementations, the control unit receives the interelectrode distance via manual input - e.g. an operator inputs the interelectrode distance, or inputs the values of gauges 331 & 333.

[0162] In some implementations, control unit 500 is configured to receive (e.g. determine) the interelectrode distance responsively to receiving the start input. For example, the control unit may receive the distance from a linear encoder attached to the manipulator stocks and / or to the shafts (e.g. a component of handle assembly 110).

[0163] There is therefore provided, in accordance with some implementations, a procedure 700 (performed by control unit 500) for the electroporation process described hereinabove: An interelectrode distance value is received / determined (step 710), and a start input isSNP1010-W001received (step 720). Responsively to the interelectrode distance and the start input, an iterative subroutine 730 is performed - e.g. until it is determined that sufficient electroporation has been achieved. Iterative subroutine 730 includes driving a series of electroporation pulses between the proximal electrode assembly and the distal electrode assembly by iteratively: applying an electroporation pulse by applying a voltage between the proximal electrode assembly and the distal electrode assembly (step 740); measuring a current of the pulse - i.e. the current that results from the applied voltage (step 750); responsively to the current and to the interelectrode distance value, determining a voltageceiling (step 760); and, for a subsequent pulse of the series, increasing the voltage toward the voltage-ceiling (step 770). That is, the pulse voltage is dynamically increased toward the voltage-ceiling during the series of pulses.

[0164] The series of electroporation pulses begins with an initial electroporation pulse having an initial voltage that is set by control unit 500 - e.g. responsively to a state of tool 100, and / or the interelectrode distance.

[0165] In some implementations, the series of pulses includes at least 50 (e.g. at least 70) pulses and / or no more than 150 (e.g. no more than 120) pulses, e.g. as 70-120 pulses, e.g.80-100 pulses.

[0166] In some implementations, each pulse has a duration of at least 50 (e.g. at least 70, such as at least 90) microseconds and / or no more than 150 (e.g. no more than 130, such as no more than 110) microseconds. For example, each pulse may have a duration of 90-110 microseconds.

[0167] Reference is now made to Fig. 12, which is a flow chart showing at least some steps of a technique or process 900 that may be used with the electroporation described hereinabove - e.g. for the application of electroporation pulses. This technique may be performed with system 20 and / or by control unit 500. However, it is to be understood that the scope of the present disclosure includes the use of process 900 with other tools, control units, or systems, mutatis mutandis.

[0168] The technique described with reference to Fig. 12 may allow the use of electroporation pulses having a voltage of sufficient magnitude to treat a tumor, while avoiding electrical arcing and / or excessive or unpredictable tissue damage.

[0169] Process 900 comprises control unit 500 performing a pulse application routine (PAR) 901. PAR 101 may comprise a dynamic subroutine 910 followed (e.g. automatically) by aSNP1010-W001steady subroutine 920, each of which is described hereinbelow. In some implementations, PAR 901 begins responsively to a start input 906 - e.g. pushing of a "start" button on control unit 500.

[0170] PAR 901 utilizes a voltage ceiling 904, which is the maximum voltage allowed for any electroporation pulse during the PAR.

[0171] Voltage ceiling 904 may be set manually, or may be determined by control unit 500.

[0172] Voltage ceiling 904 may be responsive to (e.g. may take into account) an interelectrode distance value (IDV) 902, indicative of the interelectrode distance.

[0173] In some implementations, the control unit receives IDV 902 via manual input - e.g. an operator inputs the IDV itself, or inputs the values of gauges 331 & 333.

[0174] In some implementations, control unit 500 is configured to receive (e.g. determine) the IDV responsively to receiving the start input, and / or from tool 100. For example, the control unit may receive the IDV from a linear encoder attached to the manipulator stocks and / or to the shafts (e.g. a component of handle assembly 110).

[0175] Voltage ceiling 904 may additionally be responsive to (e.g. may also take into account) tool data 903 - i.e. data indicative of the identity or model of the tool, or of one or more characteristics of the tool, such as dimensions of its electrodes. In some implementations, the control unit receives tool data 903 via manual input. In some implementations, control unit 500 is configured to receive (e.g. determine) the tool data responsively to receiving the start input, and / or from tool 100. For example, tool 100 may have the tool data stored thereon - e.g. in a chip or on a label that control unit is configured to read.

[0176] Voltage ceiling 904 may additionally be responsive to (e.g. may also take into account) tissue data 905 - i.e. data indicative of dimension, shape, electrical characteristics, and / or biological characteristics of the tumor and / or surrounding tissue. In some implementations, the control unit receives tissue data 905 via manual input. In some implementations, control unit 500 is configured to receive (e.g. determine) the tissue data responsively to receiving the start input - e.g. deriving the tissue data from other data, such as a computer image or electrical map of the tissue, and / or data from a previous PAR.

[0177] Voltage ceiling 904 may be set to be sufficiently high to achieve effective electroporation of the tumor while avoiding undesirable effects on surrounding tissue and / orSNP1010-W001arcing between electrodes. Nonetheless, PAR 901 provides an advantageously cautious approach by which the voltage is ramped up toward the voltage ceiling while monitoring one or more electrical characteristics of each pulse - as will now be described.

[0178] The ramping up is performed during / by dynamic subroutine 910, which may begin responsively to start input 906. Subroutine 910 comprises driving a series of electroporation pulses (a "dynamic series" of electroporation pulses) between the proximal and distal electrode assemblies, each pulse of the series having a voltage that is greater than that of the preceding pulse.

[0179] In some implementations, control unit 500 utilizes a fixed voltage for the initial pulse 912 of the dynamic series, irrespective of factors such as interelectrode distance 902, tool data 903, tissue data 905, voltage ceiling 904, a state of tool 100, etc. In other implementations, control unit 500 sets the voltage of the initial pulse responsively to one or more such factors.

[0180] For each pulse of the dynamic series, a current of the pulse is measured (914), and the control unit assesses whether certain conditions of the pulse are met (916): If the current of the pulse is below a certain current threshold (or a current-threshold-range), the voltage for the subsequent pulse of the dynamic series is increased toward the voltage ceiling (918).

[0181] This iterative process continues until (i) the voltage threshold is reached, or (ii) the current reaches the current threshold. Once these conditions are met, dynamic subroutine 910 ends and control unit 50 moves on to perform steady (or static) subroutine 920. The voltage of the final pulse of the dynamic series (i.e. the pulse whose voltage reached the voltage ceiling or whose current reached the current threshold) is defined or set by control unit 50 as the voltage that will be used in steady subroutine 920 - i.e. as a "steady voltage".

[0182] In steady subroutine 920, a series of electroporation pulses (a "steady series" of electroporation pulses) is driven between the proximal and distal electrode assemblies. Each pulse of the steady series has the steady voltage.

[0183] Therefore, according to PAR 101, the voltage ceiling (which may initially have been considered to be an optimal voltage) may not be reached. For example, the voltage used for steady subroutine 920 may be the maximum that was achieved during dynamic subroutine 910 that did not result in a threshold-exceeding current, or may be the lowest voltage whose resulting current exceeded the current threshold.SNP1010-W001

[0184] Whereas current measurement is an integral part of dynamic subroutine 910, steady subroutine 920 does inherently require current measurement. Nonetheless, in some implementations, even steady subroutine 920 may include a certain degree of current monitoring for safety - e.g. such that if arcing is sensed or predicted the PAR may be automatically terminated prematurely. If such premature termination occurs, control unit 500 may provide an alert to the user - e.g. to indicate that the PAR was not completed.

[0185] In some implementations, the steady series of steady subroutine 920 has a fixed number of pulses.

[0186] In some implementations, and as represented a 924, the number of pulses in the steady series depends on the number of pulses in the dynamic series - i.e. the number of pulses that were applied before the conditions were met. For example, control unit 500 may be pre-set with a total pulse number n for PAR 101 (i.e. a total count of (i) the pulses of the dynamic series and (ii) the pulses of the steady series), and steady subroutine 920 (and PAR 101 overall) ends upon the total pulse number being reached. For example, each start input / press of the start button may apply the pre-set total pulse number, with the number of steady-series pulses being dependent on the number of dynamic-series pulses.

[0187] For example, the control unit may be configured with a total pulse count of 90, such that a dynamic series that concluded after 5 pulses would result in the steady series having 85 pulses, whereas a dynamic series that concluded after 8 pulses would result in the steady series having 82 pulses.

[0188] In some implementations, the dynamic series is limited to a maximum number of pulses - e.g. 10, 8, or 6 pulses.

[0189] In some implementations, the number of pulses in the steady series is at least 10 times greater than the number of pulses in the dynamic series.

[0190] In some implementations, the number of pulses in the dynamic series is no more than 10 percent of the total pulse number.

[0191] In some implementations, the total pulse number is greater than 60 (e.g. greater than 80) and / or fewer than 120 (e.g. fewer than 100) - e.g. 80-100 pulses, such as 90 pulses. In some such implementations, dynamic subroutine 910 might require 3-10 pulses in the dynamic series, in which case the number of pulses in the steady series would be correspondingly 3-10 fewer than the total pulse number.SNP1010-W001

[0192] In some implementations, throughout dynamic subroutine 910 and / or steady subroutine 920 (e.g. throughout the entirety of PAR 901), control unit 500 monitors the heartbeat of the subject, and automatically applies one pulse per heartbeat, e.g. via R-wave synchronization.

[0193] In some implementations, the total pulse number is at least 50 (e.g. at least 70, such as at least 80), and / or no more than 150 (e.g. no more than 120, such as no more than 100). For example, the total pulse number may be 70-120, e.g. 80-100. In some such implementations, the total pulse number is 90 pulses.

[0194] In some implementations, each pulse has a duration of at least 50 (e.g. at least 70, such as at least 90) microseconds and / or no more than 150 (e.g. no more than 130, such as no more than 110) microseconds. For example, each pulse may have a duration of 90-110 microseconds. In some implementations, each pulse may have a duration of 100 microseconds.

[0195] In some implementations, the voltage increase between each successive pulse and the previous pulse is 100 V or greater - e.g. 250 V or greater, such as at 500 V or greater. In some implementations, the voltage increase depends on how far the previous pulse's current was below the current threshold. In some such implementations, if the previous pulse's current was below the current threshold by a first amount (e.g. up to 4A below), the successive pulse would have a voltage increase of a first magnitude (e.g. 100 V), whereas if the previous pulse's current was below the current threshold by a greater amount (e.g. more than 4A below), the successive pulse would have a voltage increase of a greater magnitude (e.g. 250 V).

[0196] In some implementations, the current threshold is 8 A. In some such implementations, if the previous pulse's current was below the current threshold by up to 4 A, the voltage is increased by 100 V for the successive pulse, whereas if the previous pulse's current was below the current threshold by more than 4 A, the voltage is increased by 250 V for the successive pulse. These current and voltage values may apply only to electrodes of a certain length (e.g. 4 mm) and / or having a certain interelectrode distance (e.g. 1 mm), and may therefore be different for electrodes having a greater length and / or a greater interelectrode distance.

[0197] In some implementations, dynamic subroutine 910 includes a logic that serves to verify adequate electrical coupling - i.e. that the tissue is providing adequate electricalSNP1010-W001coupling between electrode assembly 310 and electrode assembly 410. Inadequate electrical coupling may be indicative of one or both electrode assemblies being insufficiently inside of the tumor.

[0198] In some implementations, this verification logic may be configured do define adequate electrical coupling as supporting a pulse current that is greater than a current floor (i.e. a minimum current threshold). In some such implementations, the logic defines the electrical coupling as failing this coupling verification if two or more (e.g. three or more) consecutive pulses of dynamic subroutine 910 have a below-floor current. Upon such a failure, dynamic subroutine 910 is stopped, and the PAR is aborted - typically with a notification provided to the operator, which may prompt the operator to adjust the position of one or both electrode assemblies before attempting another PAR.

[0199] In some implementations, the current floor for this verification logic is 0.5 A.

[0200] In some implementations, process 900 is performed with a monopolar electrode system. That is, instead of one of the electrode assemblies (e.g. electrode assembly 310 or electrode assembly 10), there is a return electrode (e.g. a patch) located at an extracorporeal position, and the pulse application routine, including the dynamic and the steady series, is performed between the electrode assembly, disposed at the treatment position, and the return electrode.

[0201] Reference is now made to Fig. 13, which is a schematic flowchart of a process 950. Process 950 may be considered to be an implementation or variant of process 900, in accordance with some implementations.

[0202] In some implementations, for each successive pulse 952 of the dynamic series the voltage may be increased, decreased, or left the same according to the measured current of the preceding pulse. If the measured current is below the current threshold, the voltage of the successive pulse is set to be greater than the voltage of the preceding pulse. If the measured current is above the current threshold, the voltage of the successive pulse is set to be less than the voltage of the preceding pulse. If the measured current is within the current threshold, the voltage of the preceding pulse is defined as a steady voltage.

[0203] Process 950 begins with driving an initial electroporation pulse (step 952). Subsequently, a current of the pulse is measured (step 954), and a decision is made according to the measured current (step 956).SNP1010-W001

[0204] If the current of the pulse significantly exceeds the current threshold, then the voltage is decreased (step 962) and the reduced voltage is defined or set as the steady voltage for the steady series of pulses / steady subroutine (964). The magnitude of the reduction may be pre-set, or may be according to the amount by which the current of the pulse exceeded the current threshold.

[0205] Relating back to 956, if the current of the pulse is below the current threshold, then a decision 958 is made regarding pulse voltage. If the voltage of the pulse has reached the voltage-ceiling, then that voltage (i.e. the voltage of the voltage ceiling) is defined or set as the steady voltage for steady series 964. If, however, the voltage of the pulse was below the voltage-ceiling, then the voltage is increased (step 960) for the next pulse of the dynamic series.

[0206] Reference is again made to Figs. 12-13. In some implementations, the voltage increase during the dynamic series is performed in fixed increments - i.e. every increase has the same magnitude. In some implementations, the voltage toward the voltage-ceiling is performed in variable increments. In some implementations, each increase in voltage is at least partially based on the interelectrode distance. In some implementations, each increase in voltage is at least partially based on a dimension of at least one of the electrode assemblies. That is, the increase in voltage between successive pulses may be done responsively to data indicative of the interelectrode distance and / or the dimension of the electrode assembly(s).

[0207] In some implementations, the conditions of process 950 (i.e. steps 956 and / or 958) can be used as the conditions of step 916 in process 900.

[0208] Reference is now made to Fig. 14 which is a schematic flowchart of a recommendation routine 1000, in accordance with some implementations. Recommendation routine 1000 may be performed by control unit 500 - e.g. subsequently to (e.g. automatically following) a pulse application routine such as PAR 901.

[0209] The recommendation routine may include receiving information indicative of at least one of (a) an effectiveness of the pulse application routine, and (b) a geometry of the tumor. The recommendation routine may further include, responsively to the information and to the interelectrode distance, outputting a recommendation selected from the group consisting of: (i) a recommendation to change (e.g. increase or decrease) the interelectrode distance and subsequently initiate an additional pulse application routine, (ii) a recommendation to reposition the distal region and subsequently initiate an additional pulse application routine;SNP1010-W001(iii) a recommendation to initiate an additional pulse application routine by providing the start input without repositioning either of the electrode assemblies; and / or (iv) a recommendation not to initiate an additional pulse application routine.

[0210] For example, and as shown in Fig. 14, routine 1000 may include a subroutine 1002. Subroutine 1002 receives data indicative of a state of the tumor (step 1004). The state of the tumor may include the size, dimensions, position, orientation, or any other information regarding the tumor. The received information may be updated from time to time during routine 1000. Subroutine 1002 further receives data indicative of the interelectrode distance (step 1006). In some implementations subroutine 1002 also receives data indicative of the electrode position. According to data received and any other data that might be provided to the subroutine, a decision 1008 is made whether to recommend continuing with another PAR or stopping electroporation (e.g. ending the procedure). If it is determined that further electroporation is advantageous, then at least one recommendation from selection box 1010 is outputted: (a) adjusting the interelectrode distance (e.g. increasing or decreasing the distance between the electrode assemblies) for an additional PAR (recommendation 1012), (b) adjusting the position of one or more of the electrodes for an additional PAR (recommendation 1014) (e.g. a recommendation to reposition the distal region), and (c) retaining the interelectrode distance and / or electrode position(s) for an additional PAR (recommendation 1016).

[0211] The operating physician may then act responsively to the outputted recommendation (e.g. by manipulating tool 100), and then provide the start input again in order to activate control unit 500 to perform process 900 again.

[0212] In some implementations, decision 1008 is made responsively to determining a change in current between the start of the PAR and the end of the PAR. For example, control unit 500 may store in memory a pre-treatment pulse-current (e.g. the current of the first pulse of the PAR, or the current of the first pulse of the steady series of the PAR) and compare it with a post-treatment pulse-current (e.g. the current of the final pulse of the PAR). For example, the post-treatment pulse-current being different from (e.g. smaller than) the pretreatment pulse-current by less than a threshold difference may be indicative of insufficient electroporation, and control unit may output recommendation 1016. In some implementations, this threshold difference is 10 percent.

[0213] In some implementations, decision 1008 is made responsively to determining a change in a magnitude of bioimpedance between the start of the PAR and the end of theSNP1010-W001PAR. For example, control unit 500 may store in memory a pre-treatment bioimpedance magnitude (e.g. measured before the PAR, such as during positioning of the electrodes as described hereinabove) and compare it with a post-treatment bioimpedance magnitude (e.g. measured after the PAR, while the electrodes remain in place). For example, the posttreatment bioimpedance magnitude being different from (e.g. greater than) the pre-treatment bioimpedance magnitude by less than a threshold difference may be indicative of insufficient electroporation, and control unit may output recommendation 1016. In some implementations, this threshold difference is 10 percent.

[0214] In some implementations, both the pre-treatment-to-post-treatment change in current and the pre-treatment-to-post-treatment change in bioimpedance magnitude are determined. In such implementations, decision 1008 may be made responsively to both. For example, control unit may output recommendation 1016 responsively to either one (or both) of these differences being below their threshold difference.

[0215] Returning to decision 1008, if it is determined that electroporation is complete, then a "stop" command is given by the control unit (step 1018) and routine 1000 ends.

[0216] Reference is now made to Figs. 15A-G, which are schematic illustrations showing some steps of an example technique in which system 20 is used to treat a subject 10, in accordance with some implementations. For some implementations, this technique may be considered to be a variant of that described with reference to Figs. 8A-9. Features and steps of this technique may be combined with those of that described with reference to Figs. 8A-9, mutatis mutandis.

[0217] As shown in Figs. 15A-B, distal region 104 is advanced and manipulated such that at (e.g. within) tumor 4, an initial interelectrode distance d415ais formed between electrodes 314 and 414 (i.e. between electrode assemblies 310 and 410). In the example shown, this is achieved by first penetrating shaft 320 into the tumor such that electrode assembly 310 straddles (e.g. electrodes 312 and 314 straddle) the proximal boundary of the tumor (e.g. facilitated by bioimpedance sensing as described hereinabove) (Fig. 15 A), and then advancing shaft 420 out of shaft 320 until interelectrode distance d415a is achieved (Fig.15B). Electroporation is then performed at that interelectrode distance (Fig. 15C) - e.g. by operating control unit 500 to perform one of the electroporation / pulse application routines described hereinabove. For example, PAR 901 may be performed at this interelectrode distance.SNP1010-W001

[0218] Initial interelectrode distance d415a may be a minimum recommended distance for application of electroporation pulses between electrode assemblies 310 and 410 - e.g. in order to reduce a chance of arcing. This minimum recommended distance may be dependent on the axial length of electrode 314 and / or electrode 414. For example, for some variants of tool 100 in which each of electrodes 314 & 414 has an axial length of 4 mm, distance d415a is 1 mm, for some variants in which each of electrodes 314 & 414 has an axial length of 7 mm, distance d415a is 2 mm, and for some variants in which each of electrodes 314 & 414 has an axial length of 10 mm, distance d415a is 3 mm. Which variant is selected for use in a given case may depend on the size and / or position of the tumor.

[0219] In some implementations, guidance to achieve distance d415a is provided by the proximal region of tool 100 (e.g. by gauges). However, in some implementations, distal region 104 of tool 100 is configured to provide such guidance. For example, distal region 104 may be configured to provide a discrete fluoroscopically-discernable indication that distance d415a has been attained. An example of such fluoroscopically-discernable indication is now described.

[0220] Electrodes 314 and 312 are typically radiopaque. However, at the region between these electrodes (e.g. at insulator 311), shaft 320 may be radiolucent, thereby defining a radiolucent window 301 between electrodes 314 and 312. In some implementations, electrode 412 may be defined by an uncovered / uncoated distal portion of a radiopaque tubular structure, wherein a proximal portion 412' of the tubular structure is covered / coated by insulator 411. Thus, proximal portion 412' does not itself serve as an electrode, but rather serves as a conductor portion via which electrode 412 is electrically connected to connector 460 (e.g. to a terminal thereof) - e.g. by being connected to wire 413 that extends proximally from a proximal end 416 of the conductor portion (see also Fig. 6A). The tubular structure (e.g. the conductor portion thereof) extends proximally beyond electrode 414.

[0221] The tubular structure may be provided with an axial length and / or axial position with respect to electrode 414 that facilitates fluoroscopically-guided attaining of a pre-defined interelectrode distance (e.g. distance d415a). For example, and as shown, the tubular structure vacates at least part of window 301 when interelectrode distance d415a is attained. Each of Figs. 15A and 15B include a primary inset showing window 301 in close-up, and a secondary inset that schematically represents a fluoroscopic image of the window. In Fig.15A (e.g. prior to advancement of shaft 420 out of shaft 320), proximal portion 412' of the tubular structure extends proximally beyond electrode 314 and at least as far as electrodeSNP1010-W001312, thereby spanning window 301 as a fluoroscopically bridge 303 between electrodes 314 and 312. In Fig. 15B, shaft 420 has been advanced sufficiently that the tubular structure no longer reaches electrode 312, and has vacated at least part of window 301, resulting in a fluoroscopic gap 305 between electrodes 314 and 312. In the example shown, the fluoroscopically-discernable indication that interelectrode distance d415a has been attained is the presence of proximal end 416 of the tubular structure (i.e. of conductor portion 412' thereof) within window 301. This may advantageously provide a reliable indication not just that shaft 420 has been advanced sufficiently, but also that it has not been advanced too far. However, in other implementations, tool 100 may be configured such that the complete absence of the tubular structure within the window is the fluoroscopically-discernable indication.

[0222] In some implementations, electrode 412 is more radiopaque than electrode 314. For example, electrode 412 may be made of Pt / Ir, while electrode 314 may be made of stainless steel. This may allow viewing electrode 412 through electrode 314. This may be advantageous for accurate measurements of spacing between the electrodes, complying with a safety threshold of interelectrode distance.

[0223] In some implementations, the known axial length and radiopacity of electrode 412 can be utilized in calibration or interpretation of a fluoroscopy image, for example, correcting geometric distortion or determining the angle of shaft 420 with respect to the fluoroscope. That is, by knowing the length of electrode 412 and viewing the electrode via fluoroscopic imaging, determination of an angle of attack and / or position of the electrode(s) inside the tumor is deducible.

[0224] In order to cover further parts of the tumor, shaft 420 is further telescopically extended distally from shaft 320, such that electrode 414 becomes repositioned within the tumor, thereby creating an increased interelectrode distance d415b (Fig. 15D), at which another set of electroporation pulses is driven between the electrodes (e.g. another performance of process 900 / PAR 901) (Fig. 15E). In some implementations, this may be performed responsively to a recommendation (e.g. recommendation 1012) of subroutine 1002.

[0225] Figs. 15F-G show a yet further increased interelectrode distance d415c at which yet another set of electroporation pulses is driven (e.g. process 900 / PAR 901 is performed yet again). In the example shown, at distance d415c electrode assembly 410 straddles (e.g.SNP1010-W001electrodes 412 and 414 straddle) the distal boundary of the tumor. This positioning may be facilitated by bioimpedance sensing as described hereinabove.

[0226] In some implementations, rather than progressively increasing the interelectrode distance during the procedure (e.g. beginning at the minimum recommended interelectrode distance), the inter el ectrode distance is progressively decreased during the procedure (e.g. ending at the minimum recommended interelectrode distance). For example, prior to / for the first PAR, distal region 104 may be positioned such that electrode assembly 310 straddles the proximal boundary of the tumor and electrode assembly 410 straddles the distal boundary of the tumor (e.g. as described with reference to Figs. 8A-G), with subsequent PARs being performed at smaller interel ectrode distances - e.g. following movement of one or both of the electrode assemblies deeper into the tumor.

[0227] The technique described with reference to Figs. 15 A-G may advantageously facilitate electroporation coverage from the proximal boundary of the tumor to the distal boundary of the tumor somewhat irrespective of tumor "length" (i.e. dimension along the tool axis). Moreover, adjusting the interelectrode distance can advantageously shape the field of the electroporation pulses - e.g. adjusting their radial extent- e.g. to account for different tumor "widths" - i.e. dimension perpendicular to, and / or away from, the tool axis. For example, the field may be oblate (Fig. 15C) or prolate (Fig. 15G).

[0228] Though the electroporation process described with reference to Figs. 15 A-G incorporated only three positions of electrode 414, it is to be understood that electrode 414 can be repositioned less or more times as shown. In some implementations, electrode 314 can be repositioned during the electroporation process (e.g., in addition or alternatively to electrode 414). In some implementations, the electrode assemblies may include different sizes, shorter or longer, of electrodes 314 and 414.

[0229] In some implementations, the electroporation pulses may be applied between electrodes 314 and 414 (e.g., without using electrodes 312 and 412 to perform the electroporation). In some such implementations, electrodes 312 and 412 can be used to perform sensing for subsequent positioning of the electroporation electrodes 314 and 414 within the tumor. In some implementations, no sensing is performed, thereby obviating the need for electrodes 312 and 412. Procedure 700 may be utilized in other electroporation systems, mutatis mutandis.SNP1010-W001

[0230] In some implementations, while in the positioning mode, first electrode assembly 310 alone serves to perform sensing for subsequent positioning of electrodes 312 and 314 in the treatment position. And, while in the electroporation mode, electrode assembly 310 alone (i.e. without the use of electrode assembly 410) is used (i.e. in its entirety) as an electroporation electrode. For example, in some such implementations, tool 100 may not have electrode assembly 410 and / or shaft 420.

[0231] In some implementations, while in the positioning mode, first electrode assembly 410 alone serves to perform sensing for subsequent positioning of electrodes 412 and 414 in the treatment position. And, while in the electroporation mode, electrode assembly 410 alone (i.e. without the use of electrode assembly 310) is used (i.e. in its entirety) as an electroporation electrode. For example, in some such implementations, tool 100 may not have electrode assembly 310 and / or shaft 320.

[0232] In some implementations in which tool 100 omits one of electrode assembly 310 or 410, system 20 may include a third electrode - e.g. for use with electrode assembly 310 and / or 410 for the electroporation.

[0233] In some such implementations, this third electrode may be part of tool 100 - e.g. being disposed proximal to or distal from the first and / or second electrode assembly. This third electrode may be at a fixed distance or an adjustable distance to the electrode assembly.

[0234] Alternatively, this third electrode may be a skin-patch electrode - e.g. tool 100 may be for use with a skin-patch electrode, and control unit 500 is configured to apply the electroporation pulse between one or more electrodes (e.g. an electroporation electrode) of the tool and the skin-patch electrode. The skin-patch electrode may be a component of a skin-patch electrode assembly that is connectable to control unit 500. For example, a skin patch may comprise multiple skin-patch electrodes.

[0235] It is to be understood that any of the routines, subroutines, or other software or functionality described for control unit 500 may be utilized with any of the procedures described as being performed with tool 100, mutatis mutandis.

[0236] Any of the techniques, methods, operations, steps, etc. described or suggested herein can be performed on a living animal (e.g., human, other mammal, etc.) or on a non-living simulation, such as a cadaver, a cadaver lung, an anthropomorphic ghost, and / or a simulator device (which may include computerized and / or physical representations of body parts, tissue, etc.).SNP1010-W001

[0237] Any of the various systems, assemblies, devices, components, apparatuses, etc. in this disclosure can be sterilized (e.g., with heat, radiation, ethylene oxide, hydrogen peroxide, etc.) to ensure they are safe for use with patients, and the methods herein can comprise (or additional methods comprise or consist of) sterilization of the associated system, device, component, apparatus, etc. (e.g., with heat, radiation, ethylene oxide, hydrogen peroxide, etc.). Furthermore, the scope of the present disclosure includes, in some implementations, sterilizing one or more of any of the various systems, devices, apparatuses, etc. in this disclosure.

[0238] Although the operations of some of the disclosed methods are described in a particular, sequential order for convenient presentation, it should be understood that this manner of description encompasses rearrangement, unless a particular ordering is required by specific language set forth herein. For example, operations described sequentially can in some cases be rearranged or performed concurrently. Moreover, for the sake of simplicity, the attached figures may not show the various ways in which the disclosed systems, apparatuses, devices, methods, etc. can be used in conjunction with other systems, apparatuses, devices, methods, etc.

[0239] The present invention is not limited to the examples that have been particularly shown and described hereinabove. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described hereinabove, as well as variations and modifications thereof that are not in the prior art, which would occur to persons skilled in the art upon reading the foregoing description.

Claims

SNP1010-W001CLAIMS1. A system for use with a tumor within a subject, the system comprising:a tool having an extracorporeal proximal region and a distal region, the tool comprising, at the distal region:a proximal electrode assembly comprising a first proximal electrode mounted on a first shaft of the tool and a second proximal electrode mounted on the first shaft at a fixed position distal to the first proximal electrode; anda distal electrode assembly comprising a first distal electrode mounted on a second shaft of the tool and a second distal electrode mounted on the second shaft at a fixed position proximal to the first distal electrode,wherein the first shaft and the second shaft are telescopically arranged such that the second shaft is telescopically extendible distally from the first shaft in a manner that changes an axial distance between the proximal electrode assembly and the distal electrode assembly, wherein the distal region is manipulable between a provisional position in which at least one of the first proximal electrode and the first distal electrode is disposed within the tumor and a treatment position in which the first proximal electrode and the first distal electrode are disposed outside of the tumor and the second proximal electrode and the second distal electrode are disposed within the tumor; anda control unit connectable to the proximal region of the tool to electrically connect the control unit to the proximal electrode assembly and the distal electrode assembly, the control unit comprising bioimpedance-positioning circuitry and electroporation circuitry configured to:in a positioning mode, drive an electric current between the first proximal electrode and the second proximal electrode and identify, via detection of bioimpedance between the first proximal electrode and the second proximal electrode, whether the distal region is in the treatment position; andin an electroporation mode, place the first distal electrode and the second distal electrode in parallel with each other to define a distal electroporation electrode, place the first proximal electrode and the second proximal electrode in parallel with each other to define a proximal electroporation electrode, and, while the distal region is in the treatment position, drive an electroporation pulse between the distal electroporation electrode and the proximal electroporation electrode.SNP1010-W0012. The system according to claim 1, wherein the bioimpedance-positioning circuitry is configured, in the positioning mode, to define a second bioimpedance-positioning circuit by driving an electric current between the first distal electrode and the second distal electrode.

3. The system according to claim 2, wherein the control unit is configured, in the positioning mode, to identify whether the distal region is in the treatment position further via measurement of bioimpedance between the first distal electrode and the second distal electrode.

4. The system according to claim 1, wherein the control unit is configured to switch from the positioning mode into the electroporation mode by placing the first distal electrode in parallel with the second distal electrode and by placing the first proximal electrode in parallel with the second proximal electrode.

5. The system according to claim 1, wherein the distal electroporation electrode is defined by the first distal electrode and the second distal electrode together serving as the distal electroporation electrode.

6. The system according to claim 1, wherein the proximal electroporation electrode is defined by the first proximal electrode and the second proximal electrode together serving as the proximal electroporation electrode.

7. The system according to claim 1, wherein the control unit is disposed at the proximal region of the tool.

8. The system according to claim 1, wherein the tumor is in a lung of the subject.

9. A system for use with a tumor within a subject, the system comprising:a tool having an extracorporeal proximal region and a distal region, the tool comprising, at the distal region:a proximal electrode assembly comprising a first proximal electrode mounted on a first shaft of the tool and a second proximal electrode mounted on the first shaft at a fixed position distal to the first proximal electrode; anda distal electrode assembly comprising a first distal electrode mounted on a second shaft of the tool and a second distal electrode mounted on the second shaft at a fixed position proximal to the first distal electrode, wherein:the first shaft and the second shaft are telescopically arranged such that the second shaft is telescopically extendible distally from the first shaftSNP1010-W001in a manner that changes an axial distance between the distal electrode assembly and the proximal electrode assembly, andthe tool is operable to manipulate the distal region between a provisional position in which at least one of the first proximal electrode and the first distal electrode is disposed within the tumor and a treatment position in which the first proximal electrode and the first distal electrode are disposed outside of the tumor and the second proximal electrode and the second distal electrode are disposed within the tumor; anda control unit connectable to the proximal region of the tool to electrically connect the control unit to the proximal electrode assembly and the distal electrode assembly and configured, while electrically connected to the proximal electrode assembly and the distal electrode assembly, to:operate in a positioning mode in which the control unit defines a positioning circuit including the first proximal electrode and the second proximal electrode and identifies, via measurement of bioimpedance between the first proximal electrode and the second proximal electrode, whether the distal region is in the treatment position; andoperate in an electroporation mode in which the control unit defines a distal electroporation electrode by placing the first distal electrode and the second distal electrode in parallel with each other, defines a proximal electroporation electrode by placing the first proximal electrode and the second proximal electrode in parallel with each other, and, while the distal region is in the treatment position, drives an electroporation pulse between the proximal electroporation electrode and the distal electroporation electrode.

10. A system for use with a tumor within a subject, the system comprising:a tool having an extracorporeal proximal region and a distal region, the tool comprising, at the distal region:a proximal electrode assembly comprising a first proximal electrode mounted on a first shaft of the tool and a second proximal electrode mounted on the first shaft at a fixed position distal to the first proximal electrode; anda distal electrode assembly comprising a first distal electrode mounted on a second shaft of the tool and a second distal electrode mounted on the second shaft at a fixed position proximal to the first distal electrode, wherein:SNP1010-W001the first shaft and the second shaft are telescopically arranged such that the second shaft is telescopically extendible distally from the first shaft in a manner that changes an axial distance between the distal electrode assembly and the proximal electrode assembly, andthe tool is operable to manipulate the distal region between a provisional position in which at least one of the first proximal electrode and the first distal electrode is disposed within the tumor and a treatment position in which the first proximal electrode and the first distal electrode are disposed outside of the tumor and the second proximal electrode and the second distal electrode are disposed within the tumor; anda control unit connectable to the proximal region of the tool to electrically connect the control unit to the proximal electrode assembly and the distal electrode assembly, the control unit comprising bioimpedance-positioning circuitry and electroporation circuitry configured to:in a positioning mode, define a first bioimpedance-positioning circuit by driving an electric current between the first proximal electrode and the second proximal electrode, define a second bioimpedance-positioning circuit by driving an electric current between the first distal electrode and the second distal electrode, and identify, via measurement of bioimpedance between the first proximal electrode and the second proximal electrode and via measurement of bioimpedance between the first distal electrode and the second distal electrode, whether the distal region is in the treatment position; andin an electroporation mode, place the first distal electrode and the second distal electrode in parallel with each other to collectively define a distal electroporation electrode, place the first proximal electrode and the second proximal electrode in parallel with each other to collectively define a proximal electroporation electrode, and, while the distal region is in the treatment position, drive an electroporation pulse between the proximal electroporation electrode and the distal electroporation electrode.

11. A system for use with a tumor within a subject, the system comprising:a tool that has an extracorporeal proximal region and a distal region, and that comprises, at the distal region:a proximal electrode assembly, comprising:SNP1010-W001a first proximal electrode, mounted on a first shaft of the tool, and a second proximal electrode, mounted on the first shaft at a fixed position distally from the first proximal electrode; anda distal electrode assembly, comprising:a first distal electrode, mounted on a second shaft of the tool, and a second distal electrode, mounted on the second shaft at a fixed position proximally from the first distal electrode, wherein:the first shaft and the second shaft are telescopically arranged such that the second shaft is telescopically extendible distally from the first shaft in a manner that changes an axial distance between the distal electrode assembly and the proximal electrode assembly, and the tool is operable to manipulate the distal region between (a) a provisional position in which at least one of the first proximal electrode and the first distal electrode is disposed within the tumor, and (b) a treatment position in which (i) the first proximal electrode and the first distal electrode are both disposed outside of the tumor, and (ii) the second proximal electrode and the second distal electrode are both disposed within the tumor; and a control unit, connectable to the proximal region of the tool to electrically connect the control unit to the first and second electrode assemblies, and, while electrically connected to the first and second electrode assemblies, configured to:switch between:a positioning mode in which the system defines a positioning circuit in which the first proximal electrode and the second proximal electrode are in series with each other, andan electroporation mode in which the system defines an electroporation circuit in which (i) the first distal electrode and the second distal electrode are in parallel with each other to collectively define a distal electroporation electrode, and (ii) the first proximal electrode and the second proximal electrode are in parallel with each other to collectively define a proximal electroporation electrode that is in series with the distal electroporation electrode,in the positioning mode, identify, via measurement of bioimpedance between the first proximal electrode and the second proximal electrode, whether the distal region is in the treatment position, andSNP1010-W001while the distal region is in the treatment position, drive an electroporation pulse between the proximal electroporation electrode and the distal electroporation electrode.

12. The system according to claim 11, wherein:the positioning circuit is a first positioning circuit,in the positioning mode the system further defines a second positioning circuit in which the first distal electrode and the second distal electrode are in series with each other, andthe control unit is configured, in the positioning mode, to identify whether the distal region is in the treatment position via (i) measurement of bioimpedance between the first proximal electrode and the second proximal electrode, and (ii) measurement of bioimpedance between the first distal electrode and the second distal electrode.

13. A system for use with a tumor within a subject, the system comprising:a tool that has an extracorporeal proximal region and a distal region, and that comprises, at the distal region:a proximal electrode assembly, comprising:a first proximal electrode, mounted on a first shaft of the tool, and a second proximal electrode, mounted on the first shaft at a fixed position distally from the first proximal electrode; anda distal electrode assembly, comprising:a first distal electrode, mounted on a second shaft of the tool, and a second distal electrode, mounted on the second shaft at a fixed position proximally from the first distal electrode, wherein:the first shaft and the second shaft are telescopically arranged such that second shaft is telescopically extendible distally from the first shaft in a manner that changes an axial distance between the distal electrode assembly and the proximal electrode assembly, and the tool is operable to manipulate the distal region between (a) a provisional position in which at least one of the first proximal electrode and the first distal electrode is disposed within the tumor, and (b) a treatment position in which (i) the first proximal electrode and the first distal electrode are both disposed outside of the tumor, and (ii) the second proximal electrode and the second distal electrode are both disposed within the tumor; andSNP1010-W001at the proximal region, a control unit, comprising bioimpedance-positioning circuitry and electroporation circuitry, and connectable to the proximal region of the tool to electrically connect the control unit to the first and second electrode assemblies, and, while electrically connected to the first and second electrode assemblies, configured to:switch between:a positioning mode in which the bioimpedance-positioning circuitry drives an electric current between the first proximal and second proximal electrodes to identify, via detection of bioimpedance between the first proximal electrode and the second proximal electrode, whether the distal region is in the treatment position, andan electroporation mode in which the electroporation circuitry, while the distal region is in treatment position, drives an electroporation pulse between (i) the first distal electrode and the second distal electrode, together serving as a distal electroporation electrode, and (ii) the first proximal electrode and the second proximal electrode, together serving as a proximal electroporation electrode.

14. The system according to claim 13, wherein:the bioimpedance-positioning circuit is a first bioimpedance-positioning circuit, in the positioning mode the system further defines a second bioimpedancepositioning circuit in which the bioimpedance-positioning circuitry drives an electric current between the first distal electrode and the second distal electrode, andthe control unit is configured, in the positioning mode, to identify whether the distal region is in the treatment position via (i) measurement of bioimpedance between the first proximal electrode and the second proximal electrode, and (ii) measurement of bioimpedance between the first distal electrode and the second distal electrode.

15. The system according to any one of claims 13-14, wherein the circuitry is configured to switch from the positioning mode into the electroporation mode by placing the first distal electrode in parallel with the second distal electrode, and placing the first proximal electrode in parallel with the second proximal electrode.

16. The system according to any one of claims 13-15, wherein the circuitry is configured to:define the distal electroporation electrode by placing first distal electrode in parallel with the second distal electrode, andSNP1010-W001define the proximal electroporation electrode by placing first proximal electrode in parallel with the second proximal electrode.

17. A system for use with a tumor within a subject, the system comprising:a tool having an extracorporeal proximal region and a distal region, the tool comprising, at the distal region:a proximal electrode assembly comprising a first proximal electrode mounted on a first shaft of the tool and a second proximal electrode mounted on the first shaft at a fixed position distal to the first proximal electrode; anda distal electrode assembly comprising a first distal electrode mounted on a second shaft of the tool and a second distal electrode mounted on the second shaft at a fixed position proximal to the first distal electrode, wherein:the first shaft and the second shaft are telescopically arranged such that the second shaft is telescopically extendible distally from the first shaft in a manner that changes an axial distance between the proximal electrode assembly and the distal electrode assembly, andthe distal region is manipulable between a provisional position in which at least one of the first proximal electrode and the first distal electrode is disposed within the tumor and a treatment position in which the first proximal electrode and the first distal electrode are disposed outside of the tumor and the second proximal electrode and the second distal electrode are disposed within the tumor; and a control unit disposed at the proximal region of the tool and electrically connected to the proximal electrode assembly and the distal electrode assembly, the control unit comprising bioimpedance-positioning circuitry and electroporation circuitry configured to:in a positioning mode, drive an electric current between the first proximal electrode and the second proximal electrode and identify, via detection of bioimpedance between the first proximal electrode and the second proximal electrode, whether the distal region is in the treatment position; andin an electroporation mode, drive an electroporation pulse between a distal electroporation electrode defined by the first distal electrode and the second distal electrode together and a proximal electroporation electrode defined by the firstSNP1010-W001proximal electrode and the second proximal electrode together while the distal region is in the treatment position.

18. The system according to claim 17, wherein the bioimpedance-positioning circuitry is configured, in the positioning mode, to drive an electric current between the first distal electrode and the second distal electrode.

19. The system according to claim 18, wherein the control unit is configured, in the positioning mode, to identify whether the distal region is in the treatment position via measurement of bioimpedance between the first proximal electrode and the second proximal electrode and via measurement of bioimpedance between the first distal electrode and the second distal electrode.

20. The system according to claim 17, wherein the control unit is configured to switch from the positioning mode into the electroporation mode by placing the first distal electrode in parallel with the second distal electrode and by placing the first proximal electrode in parallel with the second proximal electrode.

21. The system according to claim 17, wherein the distal electroporation electrode is defined by placing the first distal electrode in parallel with the second distal electrode.

22. The system according to claim 17, wherein the proximal electroporation electrode is defined by placing the first proximal electrode in parallel with the second proximal electrode.

23. The system according to claim 17, wherein the tumor is in a lung of the subject.

24. A system for use with a tumor within a subject, the system comprising:a tool having an extracorporeal proximal region and a distal region, the tool comprising, at the distal region:a proximal electrode assembly comprising a first proximal electrode mounted on a first shaft of the tool and a second proximal electrode mounted on the first shaft at a fixed position distal to the first proximal electrode; anda distal electrode assembly comprising a first distal electrode mounted on a second shaft of the tool and a second distal electrode mounted on the second shaft at a fixed position proximal to the first distal electrode,SNP1010-W001wherein the first shaft and the second shaft are telescopically arranged such that the second shaft is telescopically extendible distally from the first shaft in a manner that changes an axial distance between the proximal electrode assembly and the distal electrode assembly, wherein the distal region is manipulable between a provisional position in which at least one of the first proximal electrode and the first distal electrode is disposed within the tumor and a treatment position in which the first proximal electrode and the first distal electrode are disposed outside of the tumor and the second proximal electrode and the second distal electrode are disposed within the tumor; anda control unit disposed at the proximal region of the tool and electrically connected to the proximal electrode assembly and the distal electrode assembly, the control unit comprising bioimpedance-positioning circuitry and electroporation circuitry configured to:in a positioning mode, drive an electric current between the first proximal electrode and the second proximal electrode and determine, based on bioimpedance detected between the first proximal electrode and the second proximal electrode, whether the distal region is in the treatment position; andin an electroporation mode, place the first distal electrode and the second distal electrode in parallel with each other to define a distal electroporation electrode, place the first proximal electrode and the second proximal electrode in parallel with each other to define a proximal electroporation electrode, and drive an electroporation pulse between the distal electroporation electrode and the proximal electroporation electrode while the distal region is in the treatment position.

25. A system for use with a tumor within a subject, the system comprising:a tool that has:an extracorporeal proximal region; anda distal region:comprising a proximal electrode assembly and a distal electrode assembly, andmanipulable, from the extracorporeal region, to adjust an interelectrode distance between the proximal electrode assembly and the distal electrode assembly; anda control unit, connectable to the proximal region of the tool to electrically connect the control unit to the proximal and distal electrode assemblies, and configured to:SNP1010-W001receive a start input,receive an interelectrode distance value that is indicative of the interelectrode distance,responsively to receiving the interelectrode distance value, set a voltageceiling,responsively to the start input, performing a pulse application routine comprising:driving, between the proximal electrode assembly and the distal electrode assembly, a dynamic series of electroporation pulses beginning with an initial pulse and continuing with successive pulses, each pulse of the dynamic series having a voltage, the control unit having a respective currentrange associated with each voltage,for each pulse of the dynamic series, measuring a current of the pulse; for each successive pulse of the dynamic series, setting a voltage of the successive pulse responsively to the measured current of a preceding pulse of the dynamic series, according to:if the measured current is below a current-threshold-range, then the voltage of the successive pulse is set to be greater than the voltage of the preceding pulse,if the measured current is within the current-threshold-range, or if the voltage of the preceding pulse is equal to the voltage-ceiling, then the voltage of the successive pulse is set to be equal to the voltage of the preceding pulse and is defined as a steady voltage, and subsequently, driving, between the proximal electrode assembly and the distal electrode assembly, a steady series of electroporation pulses, each pulse of the steady series having the steady voltage.

26. The system according to claim 25, wherein, the control unit is configured to perform a recommendation routine subsequently to the pulse application routine, the recommendation routine comprising:receiving information indicative of at least one of (i) an effectiveness of the pulse application routine, and (ii) a geometry of the tumor; andresponsively to the information and to the interelectrode distance value, outputting a recommendation selected from the group consisting of:SNP1010-W001a recommendation to change the interelectrode distance and subsequently initiate an additional pulse application routine;a recommendation to reposition the distal region and subsequently initiate an additional pulse application routine;a recommendation to initiate an additional pulse application routine by providing the start input without repositioning either of the electrode assemblies; and a recommendation not to initiate an additional pulse application routine.

27. The system according to claim 25, wherein the setting is further according to: if the measured current is above the current-threshold-range, the voltage of the successive pulse is set to be less than the voltage of the preceding pulse.

28. The system according to claim 25, wherein:the pulse application routine is pre-set with a total pulse number,the control unit is configured to stop the treatment series upon a total count of (i) the pulses of the dynamic series and (ii) the pulses of the steady series reaching the total pulse number.

29. The system according to claim 25, wherein the pulse application routine is configured such that the setting of the voltage of the successive pulse to be greater than the voltage of the preceding pulse comprises setting the voltage of the successive pulse to be greater, by a variable voltage-increase increment, than the voltage of the preceding pulse.

30. The system according to claim 25, wherein the pulse application routine has a preset fixed voltage-increase increment, and wherein the pulse application routine is configured such that the setting of the voltage of the successive pulse to be greater than the voltage of the preceding pulse comprises setting the voltage of the successive pulse to be greater, by the fixed voltage-increase increment, than the voltage of the preceding pulse.

31. The system according to claim 25, wherein the pulse application routine is configured such that the setting of the voltage of the successive pulse to be greater than the voltage of the preceding pulse comprises setting the voltage of the successive pulse to be greater than the voltage of the preceding pulse by at least 200 V.

32. The system according to claim 25, wherein:the pulse application routine further comprises setting a voltage-increase increment responsively to the interelectrode distance, andSNP1010-W001the pulse application routine is configured such that the setting of the voltage of the successive pulse to be greater than the voltage of the preceding pulse comprises setting the voltage of the successive pulse to be greater, by the voltage-increase increment, than the voltage of the preceding pulse.

33. The system according to claim 25, wherein:the control unit is configured to receive dimension data indicative of a dimension of at least one of the electrode assemblies,the pulse application routine further comprises setting a voltage-increase increment responsively to the dimension data, andthe pulse application routine is configured such that the setting of the voltage of the successive pulse to be greater than the voltage of the preceding pulse comprises setting the voltage of the successive pulse to be greater, by the voltage-increase increment, than the voltage of the preceding pulse.

34. A system for use with a tumor within a subject, the system comprising:a tool that has:an extracorporeal proximal region; anda distal region:comprising a proximal electrode assembly and a distal electrode assembly, andmanipulable, from the extracorporeal region, to adjust an interelectrode distance between the proximal electrode assembly and the distal electrode assembly; anda control unit, connectable to the proximal region of the tool to electrically connect the control unit to the proximal and distal electrode assemblies, and configured to:receive a start input,receive an interelectrode distance value that is indicative of the interelectrode distance,responsively to receiving the interelectrode distance value, set a voltageceiling,responsively to the start input, performing a pulse application routine comprising:driving, between the proximal electrode assembly and the distal electrode assembly, a dynamic series of electroporation pulses, each pulse ofSNP1010-W001the dynamic series having a voltage that is greater than that of the preceding pulse, the control unit having a respective current-threshold-range associated with each voltage,for each pulse of the dynamic series, measuring a current of the pulse, responsively to a given pulse of the series having one or both of (i) a voltage equal to the voltage-ceiling, and (ii) a current within the current- threshold-range, defining the voltage of the pulse as a steady voltage, and subsequently, driving, between the proximal electrode assembly and the distal electrode assembly, a steady series of electroporation pulses, each pulse of the steady series having the steady voltage.

35. The system according to claim 34, wherein the control unit is further configured, during the dynamic series, to verify adequate electrical coupling between the proximal electrode assembly and the distal electrode assembly by determining whether a measured current of a pulse of the dynamic series is greater than a current floor.

36. The system according to claim 35, wherein the control unit is further configured to determine that the adequate electrical coupling has failed when measured currents of two or more consecutive pulses of the dynamic series are below the current floor.

37. The system according to claim 36, wherein the control unit is further configured, responsive to determining that the adequate electrical coupling has failed, to stop the dynamic series, abort the pulse application routine, and output a notification to an operator.

38. The system according to claim 37, wherein the current floor is 0.5 A.

39. The system according to claim 34, wherein:the pulse application routine is pre-set with a total pulse number,the control unit is configured to stop the treatment series upon a total count of (i) the pulses of the dynamic series and (ii) the pulses of the steady series reaching the total pulse number.

40. A system for use with a tumor within a subject, the system comprising:a tool that has:an extracorporeal proximal region; anda distal region:comprising a proximal electrode assembly and a distal electrode assembly, andSNP1010-W001manipulable, from the extracorporeal region, to adjust an interelectrode distance between the proximal electrode assembly and the distal electrode assembly; anda control unit, connectable to the proximal region of the tool to electrically connect the control unit to the proximal and distal electrode assemblies, and configured to:receive a start input,receive an interelectrode distance value that is indicative of the interelectrode distance,responsively to the start input, drive a series of electroporation pulses between the proximal electrode assembly and the distal electrode assembly by, for each pulse of the series, applying a respective voltage between the proximal electrode assembly and the distal electrode assembly, andperform an iterative process of:for a given pulse of the series, measure a current of the pulse between the proximal electrode assembly and the distal electrode assembly, and responsively to the current and to the interelectrode distance value and for a subsequent pulse of the series, changing the voltage.

41. The system according to claim 40, wherein:the series of electroporation pulses is a dynamic series of electroporation pulses, changing the voltage comprises increasing the voltage toward a pre-defined voltageceiling, andthe control unit is configured to:for each pulse of the dynamic series, measure a current of the pulse, responsively to the measured current of a given pulse of the dynamic series:designate the voltage of the given pulse as a concluding voltage, and end the iterative process, andsubsequently, drive, between the proximal electrode assembly and the distal electrode assembly, a steady series of electroporation pulses having the concluding voltage, until a total pulse count of the first series and the second series reaches a predetermined pulse count.

42. The system according to claim 40, wherein the control unit receives an initial voltage prior to driving a series of electroporation pulses between the proximal electrode assembly and the distal electrode assembly, such that applying a respective voltage between theSNP1010-W001proximal electrode assembly and the distal electrode assembly is within a threshold difference of the initial voltage.

43. The system according to claim 40, wherein the change of the voltage is changed by at least 200 volts.

44. The system according to claim 40, wherein, for each iterative step of the iterative process, the voltage is increased by a fixed amount.

45. The system according to claim 40, wherein, for each iterative step of the iterative process, the voltage is increased by a variable amount.

46. The system according to claim 40, wherein, for each iterative step of the iterative process, the voltage is increased by an amount that is according to the interelectrode distance.

47. The system according to claim 40, wherein the control unit is configured to receive dimension data indicative of a dimension of at least one of the electrode assemblies, and wherein, for each iterative step of the iterative process, the amount of the change of the voltage is responsive to the dimension data.

48. The system according to claim 40, wherein the control unit is configured to receive the interelectrode distance responsively to receiving the start input.

49. The system according to any one of claims 40-48, wherein the control unit is configured to determine the interelectrode distance responsively to receiving the start input.

50. The system according to any one of claims 40-49, wherein the control unit is configured to receive the interelectrode distance via manual input.

51. The system according to any one of claims 40-50, wherein the tool comprises a linear encoder, and wherein the control unit is configured to receive the interelectrode distance from the linear encoder.

52. The system according to any one of claims 40-51, wherein the series of electroporation pulses begins with an initial electroporation pulse whose voltage is an initial voltage, and wherein the control unit is configured to set the initial voltage.

53. The system according to claim 52, wherein the control unit is configured to set the initial voltage responsively to a state of the tool.

54. The system according to claim 52, wherein the control unit is configured to set the initial voltage responsively to the interelectrode distance.SNP1010-W00155. A method for use with a tool that has a distal portion that includes electrodes and that is intracorporeally manipulable to adjust an interelectrode distance between the electrodes, the method comprising:receiving a start input,receiving an interelectrode distance value that is indicative of the interelectrode distance,responsively to the receiving of the start input, driving a series of electroporation pulses between the electrodes, for each pulse of the series, applying a respective voltage between the electrodes, anditeratively:for a given pulse of the series, measuring a current of the pulse between the electrodes, andresponsively to the current and to the interelectrode distance value, determining a voltage-ceiling, andfor a subsequent pulse of the series, increasing the voltage toward the voltageceiling.

56. The method according to claim 55, wherein measuring a current of the pulse between the electrodes is done manually.

57. The method according to claim 55, wherein measuring a current of the pulse between the electrodes is done electromechanically.

58. The method according to any one of claims 55-57, wherein determining a voltageceiling is done manually.

59. The method according to any one of claims 55-57, wherein determining a voltageceiling is done electromechanically.

60. The method according to any one of claims 55-59, wherein increasing the voltage toward the voltage-ceiling is done manually.

61. The method according to any one of claims 55-59, wherein increasing the voltage toward the voltage-ceiling is done electromechanically.

62. A method for use with a tool that has a proximal portion that includes a control unit, and has a distal portion that includes electrodes, the method comprising:advancing the distal portion into a subject,SNP1010-W001manipulating the distal portion into a treatment position in which an interelectrode distance exists between the electrodes, andoperating the control unit to:receive an interelectrode distance value indicative of the interelectrode distance,responsively to receiving the interelectrode distance, set a voltage-ceiling, andperform a pulse application routine comprising:driving, between the electrodes, a dynamic series of electroporation pulses, each pulse of the dynamic series having a voltage that is greater than that of the preceding pulse, the control unit having a respective current- threshold-range associated with each voltage,for each pulse of the dynamic series, measuring a current of the pulse, responsively to a given pulse of the series having one or both of (i) a voltage equal to the voltage-ceiling, and (ii) a current within the current- threshold-range, defining the voltage of the pulse as a steady voltage, and subsequently, driving, between the electrodes, a steady series of electroporation pulses, each pulse of the steady series having the steady voltage.

63. The method according to claim 62, wherein:the pulse application routine is pre-set with a total pulse number, anddriving the steady series comprises driving the steady series only until a total count of (i) the pulses of the dynamic series, and (ii) the pulses of the steady series, reaches the total pulse number.

64. The method according to claim 62, wherein advancing of the electrodes is performed via an endoscope.

65. The method according to claim 62, wherein the treatment position is inside a tumor.

66. The method according to claim 65, wherein:the pulse application routine is a first pulse application routine,the dynamic series is a first dynamic series,the steady series is a first steady series,SNP1010-W001the interelectrode distance that existed between the electrodes during performance of the first pulse application routine is a first interelectrode distance, the interelectrode distance valve being a first interelectrode distance value, andsubsequently to driving the first steady series of electroporation pulses between the electrodes, the method further comprises the control unit:receiving information indicative of at least one of (i) an effectiveness of the first pulse application routine, and (ii) a geometry of the tumor; and responsively to the information and to the first interelectrode distance value, outputting a recommendation selected from the group consisting ofa recommendation to change the interelectrode distance and subsequently initiate an additional pulse application routine;a recommendation to reposition the distal portion and subsequently initiate an additional pulse application routine;a recommendation to initiate an additional pulse application routine by providing the start input without repositioning either of the electrode assemblies; anda recommendation not to initiate an additional pulse application routine.

67. The method according to any one of claims 62-65, wherein the distance between the electrodes is a coaxial distance.

68. The method according to any one of claims 62-67, wherein the distance between the electrodes is a parallel distance.

69. The method according to any one of claims 62-68, wherein providing the control unit with the electrode distance input is done manually.

70. The method according to any one of claims 62-68, wherein providing the control unit with the electrode distance input is done electromechanically.

71. The method according to any one of claims 62-70, wherein providing the control unit with a start input is done manually.

72. The method according to any one of claims 62-70, wherein providing the control unit with a start input is done electromechanically.SNP1010-W00173. A method for use with a tool that has a proximal portion including a control unit and a distal portion including electrodes, the method comprising:using the tool to advance the distal portion into a subject;using the tool to manipulate the distal portion into a treatment position in which an interelectrode distance exists between the electrodes;providing to the control unit an interelectrode distance value indicative of the interelectrode distance;causing, using the control unit and responsively to the interelectrode distance value, a voltage ceiling to be set; andcausing, using the control unit, performance of a pulse application routine comprising:driving, between the electrodes, a dynamic series of electroporation pulses, each pulse of the dynamic series having a voltage greater than that of a preceding pulse, the control unit having a respective current-threshold range associated with each voltage;for each pulse of the dynamic series, measuring a current of the pulse; responsively to a given pulse of the dynamic series having a voltage equal to the voltage ceiling or a current within the respective current-threshold range, defining the voltage of the given pulse as a steady voltage; andsubsequently driving, between the electrodes, a steady series of electroporation pulses, each pulse of the steady series having the steady voltage.

74. A method for use with a tool having a proximal portion including a control unit and a distal portion including electrodes, the method comprising:using the tool to advance the distal portion into a subject;using the tool to manipulate the distal portion into a treatment position in which an interelectrode distance exists between the electrodes;providing, to the control unit, an interelectrode distance value indicative of the interelectrode distance;causing, by operation of the control unit and responsive to the interelectrode distance value, a voltage ceiling to be set; andcausing, by operation of the control unit, performance of a pulse application routine comprising:SNP1010-W001driving, between the electrodes, a dynamic series of electroporation pulses, each pulse of the dynamic series having a voltage greater than a voltage of a preceding pulse, the control unit having a respective current-threshold range associated with the voltage of each pulse of the dynamic series;for each pulse of the dynamic series, measuring a current of the pulse; responsive to a given pulse of the dynamic series having the voltage equal to the voltage ceiling or the current within the respective current-threshold range, defining the voltage of the given pulse as a steady voltage; andsubsequently driving, between the electrodes, a steady series of electroporation pulses, each pulse of the steady series having the steady voltage.

75. The method according to claim 74, wherein causing performance of the pulse application routine comprises verifying adequate electrical coupling between the electrodes by determining whether a measured current of a pulse of the dynamic series is greater than a current floor.

76. The method according to claim 75, wherein causing performance of the pulse application routine comprises determining that the adequate electrical coupling has failed when measured currents of two or more consecutive pulses of the dynamic series are below the current floor.

77. The method according to claim 76, further comprising, responsive to determining that the adequate electrical coupling has failed, stopping the dynamic series, aborting the pulse application routine, and outputting a notification to an operator.

78. The method according to claim 77, wherein the current floor is 0.5 A.

79. The method according to claim 74, wherein providing the inter el ectrode distance value to the control unit comprises receiving a start input and responsively thereto receiving the interelectrode distance value.

80. The method according to claim 74, wherein providing the inter el ectrode distance value to the control unit comprises manually inputting the interelectrode distance value.

81. The method according to claim 74, wherein causing the voltage ceiling to be set comprises causing the voltage ceiling to be set additionally responsive to tool data indicative of an identity of the tool, a model of the tool, or one or more characteristics of the tool.SNP1010-W00182. The method according to claim 74, wherein causing the voltage ceiling to be set comprises causing the voltage ceiling to be set additionally responsive to tissue data indicative of a dimension, a shape, an electrical characteristic, or a biological characteristic of tissue.

83. The method according to claim 74, wherein the pulse application routine is pre-set with a total pulse number, and wherein the method comprises stopping the pulse application routine upon a total count of the pulses of the dynamic series and the pulses of the steady series reaching the total pulse number.

84. The method according to claim 74, wherein causing performance of the pulse application routine comprises causing the control unit to monitor a heartbeat of the subject and automatically apply one pulse per heartbeat.

85. A system for electroporation of tissue of a subject, the system comprising:a tool having a distal portion including electrodes and a proximal portion including a control unit, the electrodes being positionable such that an interelectrode distance exists between the electrodes;the control unit being configured to receive an interelectrode distance value indicative of the interelectrode distance;the control unit being further configured to set a voltage ceiling responsive to the interelectrode distance value; andthe control unit being further configured to perform a pulse application routine by:driving, between the electrodes, a dynamic series of electroporation pulses, each pulse of the dynamic series having a voltage greater than a voltage of a preceding pulse, the control unit having a respective current-threshold range associated with the voltage of each pulse of the dynamic series;for each pulse of the dynamic series, measuring a current of the pulse; responsive to a given pulse of the dynamic series having the voltage equal to the voltage ceiling or the current within the respective current-threshold range, defining the voltage of the given pulse as a steady voltage; andsubsequently driving, between the electrodes, a steady series of electroporation pulses, each pulse of the steady series having the steady voltage.

86. The system according to claim 85, wherein the control unit is further configured, during the dynamic series, to verify adequate electrical coupling between the electrodes bySNP1010-W001determining whether a measured current of a pulse of the dynamic series is greater than a current floor.

87. The system according to claim 86, wherein the control unit is further configured to determine that the adequate electrical coupling has failed when measured currents of two or more consecutive pulses of the dynamic series are below the current floor.

88. The system according to claim 87, wherein the control unit is further configured, responsive to determining that the adequate electrical coupling has failed, to stop the dynamic series, abort the pulse application routine, and output a notification to an operator.

89. The system according to claim 88, wherein the current floor is 0.5 A.

90. The system according to claim 85, wherein the control unit is configured to receive the interelectrode distance value via manual input.

91. The system according to claim 85, wherein the tool includes a linear encoder, and wherein the control unit is configured to receive the interelectrode distance value from the linear encoder.

92. The system according to claim 85, wherein the control unit is further configured to set an initial voltage of an initial pulse of the dynamic series responsively to a state of the tool or to the interelectrode distance.

93. The system according to claim 85, wherein the pulse application routine is pre-set with a total pulse number, and wherein the control unit is configured to stop the pulse application routine upon a total count of the pulses of the dynamic series and the pulses of the steady series reaching the total pulse number.

94. The system according to claim 85, wherein the control unit is configured to limit the dynamic series to a maximum of 10 pulses.

95. The system according to claim 85, wherein the control unit is configured such that each pulse of the dynamic series and each pulse of the steady series has a duration of 90 to 110 microseconds.

96. A system for use with a tumor within a subject, the system comprising a tool that comprises:a sheath assembly, comprising:a flexible sheath, having a distal part that includes a sheath opening,SNP1010-W001a sheath stock, fixed to a proximal part of the sheath, and configured to transbronchially advance the distal part of the sheath into an airway of the subject; a first manipulator assembly, comprising:a first shaft, disposed coaxially within the sheath;at a distal part of the first shaft, a proximal electrode assembly, comprising:a first proximal electrode, anda second proximal electrode, mounted at a fixed position distally from the first proximal electrode; anda first-manipulator stock, fixed to a proximal part of the first shaft, and configured to, by sliding the first shaft distally through the sheath, advance the proximal electrode assembly out of the sheath opening and through a wall of the airway toward the tumor;a second manipulator assembly, comprising:a second shaft, disposed coaxially within the first shaft;at a distal part of the second shaft, a distal electrode assembly, comprising:a first distal electrode, anda second distal electrode, mounted at a fixed position proximally from the first distal electrode; anda second-manipulator stock, fixed to a proximal part of the second shaft, and configured to, by sliding the second shaft distally through the first shaft, advance the distal electrode assembly distally out of the first shaft and through the tumor; a first fastener, at a proximal part of the tool, the first fastener being manipulable between:an unlocked state, anda locked state that inhibits sliding of the first shaft through the sheath by fastening the first-manipulator stock to the sheath stock; anda second fastener, at a proximal part of the tool, the second fastener being manipulable between:an unlocked state, anda locked state that inhibits sliding of the second shaft through the first shaft by fastening the second-manipulator stock to the first-manipulator stock.SNP1010-W00197. The system according to claim 96, wherein the system is for use with an endoscope, and wherein the sheath is configured to be advanced through the endoscope such that a distal opening of the sheath becomes exposed out of the endoscope.

98. The system according to any one of claims 96-97, wherein the first shaft of the first manipulator assembly comprises an unsupported extension configured to limit compressive forces on the first shaft.

99. The system according to any one of claims 96-98, wherein the first shaft of the first manipulator assembly comprises an unsupported extension configured to absorb shocks acting upon the first shaft.

100. The system according to any one of claims 96-99, wherein the second shaft of the second manipulator assembly comprises an unsupported extension configured to limit compressive forces on the second shaft.

101. The system according to any one of claims 96-100, wherein the second shaft of the second manipulator assembly comprises an unsupported extension configured to absorb shocks acting upon the second shaft.

102. The system according to any one of claims 96-101, wherein the sheath stock is distal to the second-manipulator stock.

103. The system according to any one of claims 96-102, wherein the tool comprises a gauge indicating an axial position of the first-manipulator stock relative to the sheath stock.

104. The system according to any one of claims 96-103, wherein the tool comprises a gauge indicating an axial position of the second-manipulator stock relative to the first-manipulator stock.

105. The system according to any one of claims 96-104, wherein an axial position of the first-manipulator stock relative to the sheath stock is manually adjustable.

106. The system according to any one of claims 96-104, wherein an axial position of the first-manipulator stock relative to the sheath stock is electromechanically adjustable.

107. The system according to any one of claims 96-105, wherein an axial position of the first-manipulator stock relative to the second-manipulator stock is manually adjustable.SNP1010-W001108. The system according to any one of claims 96-105, wherein an axial position of the first-manipulator stock relative to the second-manipulator stock is electromechanically adjustable.

109. The system according to any one of claims 96-108, wherein the first fastener comprises a set-screw mounted on the sheath stock, and manipulable to the locked state by screwing into contact with the first-manipulator stock.

110. The system according to any one of claims 96-109, wherein the second fastener comprises a set-screw mounted on the second-manipulator stock, and manipulable to the locked state by screwing into contact with the first-manipulator stock.

111. The system according to any one of claims 96-110, wherein the first fastener comprises a pin mounted on the sheath stock, and manipulable to the locked state by pushing into a pinhole defined in the first-manipulator stock.

112. The system according to any one of claims 96-111, wherein the second fastener comprises a pin mounted on the second-manipulator stock, and manipulable to the locked state by pushing into a pinhole defined in the first-manipulator stock.

113. The system according to any one of claims 96-112, wherein the first fastener is manually manipulable.

114. The system according to any one of claims 96-113, wherein the second fastener is manually manipulable.

115. The system according to any one of claims 96-112, wherein the first fastener is electromechanically manipulable.

116. The system according to any one of claims 96-112, wherein the second fastener is electromechanically manipulable.

117. The system according to any one of claims 96-116, wherein the second proximal electrode is shaped to define a hollow needle.

118. The system according to any one of claims 96-117, wherein the first-manipulator stock is slidable into the sheath stock and slidable into the second-manipulator stock.

119. The system according to claim 118, wherein the first-manipulator stock is:slidable distally into the sheath stock to slide the first shaft distally through the sheath, andSNP1010-W001slidable proximally into the second-manipulator stock to slide the second shaft distally through the first shaft.

120. The system according to claim 119, wherein an axial position of the first stock relative to the second stock is adjustable manually.

121. The system according to claim 119, wherein an axial position of the first stock relative to the second stock is adjustable electromechanically.

122. A system for use with a tumor within a subject, the system comprising:a tool that has an extracorporeal proximal region and a distal region, and that comprises, at the distal region:an electrode assembly, comprising:a first electrode, mounted on a shaft of the tool, anda second electrode, mounted on the shaft at a fixed position distally from the first electrode; wherein:the tool is operable to manipulate the distal region into a treatment position in which (i) the first electrode is disposed outside of the tumor, and (ii) the second electrode is disposed within the tumor; anda control unit, connectable to the proximal region of the tool to electrically connect the control unit to the electrode assembly, and, while electrically connected to the electrode assembly, configured to:switch between:a positioning mode in which the system defines a positioning circuit in which the first electrode and the second electrode are in series with each other, andan electroporation mode in which the system defines an electroporation circuit in which the first electrode and the second electrode are in parallel with each other to collectively define an electroporation electrode,in the positioning mode, identify, via measurement of bioimpedance between the first electrode and the second electrode, whether the distal region is in the treatment position, andSNP1010-W001while the distal region is in the treatment position, drive the electroporation electrode to apply an electroporation pulse.

123. The system according to claim 122, wherein:the electrode assembly is a first electrode assembly,the tool comprises, at the distal region, a second electrode assembly, and the control unit is configured to apply the electroporation pulse between the electroporation electrode and the second electrode assembly.

124. The system according to claim 123, wherein the second electrode assembly comprises exactly one electrode, and the control unit is configured to apply the electroporation pulse between the electroporation electrode of the first electrode assembly and the exactly one electrode of the second electrode assembly.

125. The system according to claim 123, wherein:the second electrode assembly comprises a first second-assembly electrode and a second second-assembly electrode, andthe control unit is configured:to place the first second-assembly electrode and the second second-assembly electrode in series with each other upon switching to the positioning mode, and to place the first second-assembly electrode and the second second-assembly electrode in parallel with each other upon switching to the electroporation mode.

126. The system according to any one of claims 123-125, wherein the second electrode assembly is proximal to the first electrode assembly.

127. The system according to any one of claims 123-125, wherein the second electrode assembly is distal to the first electrode assembly.

128. The system according to any one of claims 123-127, wherein the second electrode assembly is mounted at a fixed axial distance from the first electrode assembly.

129. The system according to any one of claims 123-127, wherein the tool is configured to facilitate adjustment of an axial distance between the first electrode assembly and the second electrode assembly.

130. The system according to any one of claims 123-129, wherein:the system is for use with a skin-patch electrode, andSNP1010-W001the control unit is configured to apply the electroporation pulse between the electroporation electrode and the skin-patch electrode.

131. A method for use with a tool having a distal portion that includes electrodes, the method comprising, on a data-processing system:receiving a first interelectrode distance value indicative of an interelectrode distance that existed between the electrodes during performance of a first pulse application routine, receiving information indicative of at least one of (i) an effectiveness of the first pulse application routine, and (ii) a geometry of the tumor; andresponsively to the information and to the first interelectrode distance value, outputting a recommendation selected from the group consisting ofa recommendation to change the interelectrode distance and subsequently initiate an additional pulse application routine;a recommendation to reposition the distal region and subsequently initiate an additional pulse application routine;a recommendation to initiate an additional pulse application routine by providing the start input without repositioning either of the electrode assemblies; and a recommendation not to initiate an additional pulse application routine.

132. A system for use with a tumor within a subject, the system comprising:a tool that has:an extracorporeal proximal region; anda distal region, comprising an electrode assembly; anda control unit, connectable to the proximal region of the tool to electrically connect the control unit to the electrode assembly, and configured to:receive a start input,receive a voltage-ceiling,responsively to the start input, performing a pulse application routine comprising:driving, a dynamic series of electroporation pulses via the electrode assembly, each pulse of the dynamic series having a voltage that is greater than that of the preceding pulse, the control unit having a respective current- threshold-range associated with each voltage,for each pulse of the dynamic series, measuring a current of the pulse,SNP1010-W001responsively to a given pulse of the series having one or both of (i) a voltage equal to the voltage-ceiling, and (ii) a current within the current- threshold-range, defining the voltage of the pulse as a steady voltage, and subsequently, driving a steady series of electroporation pulses via the electrode assembly, each pulse of the steady series having the steady voltage.

133. The system according to claim 132, wherein:the pulse application routine is pre-set with a total pulse number,the control unit is configured to stop the treatment series upon a total count of (i) the pulses of the dynamic series and (ii) the pulses of the steady series reaching the total pulse number.

134. A system for use with a tumor within a subject, the system comprising:a tool that has:an extracorporeal proximal region; anda distal region, comprising an electrode assembly; anda control unit, connectable to the proximal region of the tool to electrically connect the control unit to the electrode assembly, and configured to:receive a start input,responsively to the start input, perform a pulse application routine comprising:driving a dynamic series of electroporation pulses via the electrode assembly beginning with an initial pulse and continuing with successive pulses, each pulse of the dynamic series having a voltage, the control unit having a respective current-range associated with each voltage, for each pulse of the dynamic series, measuring a current of the pulse, for each successive pulse of the dynamic series, setting a voltage of the successive pulse responsively to the measured current of a preceding pulse of the dynamic series, according to:if the measured current is below a current-threshold-range, the voltage of the successive pulse is set to be greater than the voltage of the preceding pulse,SNP1010-W001if the measured current is within the current-threshold-range, the voltage of the successive pulse is set to be equal to the voltage of the preceding pulse and is defined as a steady voltage, and subsequently, driving a steady series of electroporation pulses via the electrode assembly, each pulse of the steady series having the steady voltage.

135. The system according to claim 134, wherein:the pulse application routine is pre-set with a total pulse number,the control unit is configured to stop the treatment series upon a total count of (i) the pulses of the dynamic series and (ii) the pulses of the steady series reaching the total pulse number.

136. Apparatus, for use with a tissue of a subject, apparatus comprising a tool that comprises:at a proximal region of the tool, at least one electrical terminal for electrically connecting the terminal to a control unit;a set of wires extending from the electrical terminal to a distal region of the tool; and at a distal region of the tool:a first shaft, having a first electrode assembly comprising:a first first-shaft electrode, radiopaque, mounted on the first shaft, a second first-shaft electrode, being radiopaque, and mounted on the first shaft at a fixed position proximally from the first first-shaft electrode such that the first shaft defines a radiolucent window between the first and second first-shaft electrodes, anda second shaft, having a second electrode assembly, comprising:a radiopaque tubular structure, mounted on the second shaft of the tool,a tubular insulator, covering a proximal portion of the tubular structure but not a distal portion of the tubular structure, thereby defining (i) the uncovered distal portion as a first second-shaft electrode, and (ii) the covered proximal portion as a conductor portion, anda second second-shaft electrode, mounted on the second shaft at a fixed position in which (i) the second second-shaft electrode is disposed coaxially around the tubular insulator proximally from the first second-shaftSNP1010-W001distal electrode, and (ii) the conductor portion extends from the first second- shaft electrode proximally beyond the second second-shaft electrode, wherein:each of the first first-shaft electrode, the second first-shaft electrode, and the second second-shaft electrode is independently connected to the terminal by being connected to a respective wire of the set,the first second-shaft electrode is independently connected to the terminal by the conductor portion being connected to a respective wire of the set,the second shaft is telescopically extendible distally out of the first shaft in a manner that axially moves the second electrode assembly with respect to the first electrode assembly, andthe tubular structure has an axial length that facilitates fluoroscopically-guided axial movement of the second electrode assembly with respect to the first electrode assembly to attain a pre-defined axial distance between the first first-shaft electrode and the second second-shaft electrode by, at the pre-defined axial distance, a proximal end of the conductor being fluoroscopically visible in the radiolucent window.

137. The system according to claim 136, wherein:attaining the pre-defined axial distance, between the first first-shaft and second second-shaft electrodes, creates a second axial distance, between the second first-shaft electrode and the proximal end of the conductor, that is correlative to the first axial distance, andthe second axial distance is fluoroscopically visible.

138. Apparatus, for use with a tissue of a subject, the apparatus comprising a tool that comprises:at a proximal region of the tool, at least one electrical terminal for electrically connecting the terminal to a control unit;a set of wires extending from the electrical terminal to a distal region of the tool; and a first shaft;a second shaft; andat a distal region of the tool:a first first-shaft electrode, radiopaque, mounted on the first shaft, a second first-shaft electrode, being radiopaque, and mounted on the first shaft at a fixed position proximally from the first first-shaft electrode such that theSNP1010-W001first shaft defines a radiolucent window between the first and second first-shaft electrodes,a radiopaque tubular structure, mounted on the second shaft of the tool, and having a distal end and a proximal end, anda tubular insulator, covering a proximal portion of the tubular structure but not a distal portion of the tubular structure, thereby defining (i) the uncovered distal portion as a second-shaft electrode, and (ii) the covered proximal portion as a conductor portion that extends proximally from the second-shaft electrode, wherein:the first first-shaft electrode and the second first-shaft electrode are connected to the terminal by being connected to respective wires of the set,the second-shaft electrode is connected to the terminal by the conductor portion being connected to a respective wire of the set,the second shaft is telescopically extendible distally out of the first shaft, and the tubular structure has an axial length that facilitates fluoroscopically-guided axial movement of the second shaft with respect to the first shaft to attain a pre-defined axial distance between the first first-shaft electrode and the second-shaft electrode by, at the predefined axial distance, a proximal end of the conductor being fluoroscopically visible in the radiolucent window.

139. A non-transitory computer-readable medium usable and / or for use with a control unit, the medium comprising instructions that, when executed by one or more processors of the control unit, cause the control unit to, using a controllable switching arrangement that selectively electrically couples a plurality of intracorporeal electrodes of a medical tool: operate in a positioning mode in which at least two of the plurality of intracorporeal electrodes are electrically coupled in series and a bioimpedance measurement obtained using the at least two series-coupled electrodes is used to determine whether the plurality of intracorporeal electrodes are positioned in a treatment geometry relative to a boundary of target tissue; andresponsive to determining that the treatment geometry is achieved, operate in an electroporation mode in which the at least two of the plurality of intracorporeal electrodes are electrically coupled in parallel to collectively define an electroporation electrode and cause delivery of a plurality of electroporation pulses using respective pulse voltages thatSNP1010-W001are adaptively controlled based on a measured pulse current and an interel ectrode distance value indicative of spacing between electrodes used for delivering the electroporation pulses such that the respective pulse voltages are constrained by a voltage ceiling determined from the measured pulse current and the interelectrode distance value.

140. A computer-implemented method, executed by a control unit, for controlling application of electroporation pulses between a proximal electrode assembly and a distal electrode assembly, the method comprising:receiving a start input and establishing, based on at least one of an interelectrode distance, tool data, or tissue data, a voltage ceiling for a pulse application routine;driving, during a dynamic subroutine, a dynamic series of electroporation pulses between the proximal electrode assembly and the distal electrode assembly;measuring, for each electroporation pulse of the dynamic series, a current of the electroporation pulse;in response to the current being below a current threshold and a voltage of the electroporation pulse being below the voltage ceiling, increasing a voltage of a successive electroporation pulse toward the voltage ceiling;in response to the current reaching the current threshold, defining the voltage of the electroporation pulse as a steady voltage;in response to the current exceeding the current threshold, decreasing the voltage relative to the voltage of the electroporation pulse and defining the decreased voltage as the steady voltage;in response to the voltage of the electroporation pulse reaching the voltage ceiling while the current is below the current threshold, defining the voltage ceiling as the steady voltage; anddriving, during a steady subroutine, a steady series of electroporation pulses between the proximal electrode assembly and the distal electrode assembly, each electroporation pulse of the steady series having the steady voltage.

141. The computer-implemented method according to claim 128, further comprising, during the dynamic subroutine, verifying adequate electrical coupling between the proximal electrode assembly and the distal electrode assembly by determining whether a measured current of an electroporation pulse of the dynamic series is greater than a current floor.SNP1010-W001142. The computer-implemented method according to claim 128A, further comprising determining that the adequate electrical coupling has failed when measured currents of two or more consecutive electroporation pulses of the dynamic series are below the current floor.

143. The computer-implemented method according to claim 128B, further comprising, responsive to determining that the adequate electrical coupling has failed, stopping the dynamic subroutine, aborting the pulse application routine, and outputting a notification to an operator.

144. The computer-implemented method according to claim 128C, wherein the current floor is 0.5 A.

145. A computer-implemented method, executed by a control unit, for controlling application of electroporation pulses between a proximal electrode assembly and a distal electrode assembly, the computer-implemented method comprising:establishing a voltage ceiling for a pulse application routine;driving, during a dynamic series, electroporation pulses between the proximal electrode assembly and the distal electrode assembly;measuring a current of each electroporation pulse of the dynamic series;in response to the current of a pulse of the dynamic series being below a current threshold and a voltage of the pulse being below the voltage ceiling, increasing a voltage of a successive electroporation pulse of the dynamic series;in response to the current of the pulse of the dynamic series being above the current threshold, decreasing the voltage of the successive electroporation pulse;in response to the current of the pulse of the dynamic series being within a current threshold range, defining the voltage of the pulse of the dynamic series as a steady voltage;in response to the voltage of the pulse of the dynamic series reaching the voltage ceiling while the current of the pulse of the dynamic series is below the current threshold, defining the voltage ceiling as the steady voltage; anddriving, during a steady series, electroporation pulses between the proximal electrode assembly and the distal electrode assembly at the steady voltage.

146. The computer-implemented method according to claim DPIP3, wherein establishing the voltage ceiling comprises determining the voltage ceiling responsively to an interelectrode distance value indicative of an interelectrode distance.SNP1010-W001147. The computer-implemented method according to claim DPIP3, wherein establishing the voltage ceiling comprises determining the voltage ceiling responsively to tool data indicative of an identity, a model, or an electrode dimension of a tool.

148. The computer-implemented method according to claim DPIP3, wherein establishing the voltage ceiling comprises determining the voltage ceiling responsively to tissue data indicative of a dimension, a shape, an electrical characteristic, or a biological characteristic of tissue.

149. The computer-implemented method according to claim DPIP3, wherein driving the electroporation pulses during the dynamic series comprises driving an initial electroporation pulse at a fixed initial voltage irrespective of at least one of an interelectrode distance, tool data, tissue data, or the voltage ceiling.

150. The computer-implemented method according to claim DPIP3, wherein increasing the voltage of the successive electroporation pulse comprises selecting a magnitude of increase according to an amount by which the current of the pulse of the dynamic series is below the current threshold.

151. The computer-implemented method according to claim DPIP3, further comprising terminating the steady series when a sum of a number of pulses in the dynamic series and a number of pulses in the steady series reaches a preset total pulse count.

152. The computer-implemented method according to claim DPIP3, wherein the dynamic series is limited to a maximum of 10 pulses.

153. The computer-implemented method according to claim DPIP3, further comprising synchronizing application of the electroporation pulses to a heartbeat of a subject such that one electroporation pulse is applied per heartbeat.

154. The computer-implemented method according to claim DPIP3, wherein each electroporation pulse has a duration of 90 to 110 microseconds.

155. A control unit for controlling application of electroporation pulses between a proximal electrode assembly and a distal electrode assembly, the control unit comprising:a processor; anda memory storing instructions that, when executed by the processor, cause the control unit to:establish a voltage ceiling for a pulse application routine;SNP1010-W001drive, during a dynamic series, electroporation pulses between the proximal electrode assembly and the distal electrode assembly;measure a current of each electroporation pulse of the dynamic series;in response to the current of a pulse of the dynamic series being below a current threshold and a voltage of the pulse being below the voltage ceiling, increase a voltage of a successive electroporation pulse of the dynamic series;in response to the current of the pulse of the dynamic series being above the current threshold, decrease the voltage of the successive electroporation pulse;in response to the current of the pulse of the dynamic series being within a current threshold range, define the voltage of the pulse of the dynamic series as a steady voltage;in response to the voltage of the pulse of the dynamic series reaching the voltage ceiling while the current of the pulse of the dynamic series is below the current threshold, define the voltage ceiling as the steady voltage; anddrive, during a steady series, electroporation pulses between the proximal electrode assembly and the distal electrode assembly at the steady voltage.

156. A non-transitory computer-readable medium storing instructions that, when executed by one or more processors of a control unit, cause the control unit to perform a method for controlling application of electroporation pulses between a proximal electrode assembly and a distal electrode assembly, the method comprising:establishing a voltage ceiling for a pulse application routine;driving, during a dynamic series, electroporation pulses between the proximal electrode assembly and the distal electrode assembly;measuring a current of each electroporation pulse of the dynamic series;in response to the current of a pulse of the dynamic series being below a current threshold and a voltage of the pulse being below the voltage ceiling, increasing a voltage of a successive electroporation pulse of the dynamic series;in response to the current of the pulse of the dynamic series being above the current threshold, decreasing the voltage of the successive electroporation pulse of the dynamic series;in response to the current of the pulse of the dynamic series being within a current threshold range, defining the voltage of the pulse of the dynamic series as a steady voltage;SNP1010-W001in response to the voltage of the pulse of the dynamic series reaching the voltage ceiling while the current of the pulse of the dynamic series is below the current threshold, defining the voltage ceiling as the steady voltage; anddriving, during a steady series, electroporation pulses between the proximal electrode assembly and the distal electrode assembly at the steady voltage.

157. A computer-implemented method, executed by a control unit, for controlling application of electroporation pulses between a proximal electrode assembly and a distal electrode assembly, the computer-implemented method comprising:establishing a voltage ceiling for a pulse application routine;driving a dynamic series of electroporation pulses between the proximal electrode assembly and the distal electrode assembly;measuring a current associated with the dynamic series;adjusting a voltage of the dynamic series according to the measured current while the voltage remains subject to the voltage ceiling;identifying a steady voltage based on the dynamic series; anddriving a steady series of electroporation pulses between the proximal electrode assembly and the distal electrode assembly at the steady voltage.

158. The computer-implemented method according to claim 1, wherein establishing the voltage ceiling comprises determining the voltage ceiling responsively to an inter el ectrode distance value indicative of an interelectrode distance.

159. The computer-implemented method according to claim 1, wherein establishing the voltage ceiling comprises determining the voltage ceiling responsively to tool data indicative of an identity, a model, or a characteristic of a tool.

160. The computer-implemented method according to claim 1, wherein establishing the voltage ceiling comprises determining the voltage ceiling responsively to tissue data indicative of a dimension, a shape, an electrical characteristic, or a biological characteristic of tissue.

161. The computer-implemented method according to claim 1, wherein adjusting the voltage of the dynamic series comprises increasing a voltage of a successive electroporation pulse when the measured current is below a current threshold.SNP1010-W001162. The computer-implemented method according to claim 1, wherein adjusting the voltage of the dynamic series comprises decreasing a voltage of a successive electroporation pulse when the measured current is above a current threshold.

163. The computer-implemented method according to claim 1, wherein identifying the steady voltage comprises defining as the steady voltage a voltage of a pulse whose current reaches a current threshold.

164. The computer-implemented method according to claim 1, wherein identifying the steady voltage comprises defining as the steady voltage the voltage ceiling when the voltage ceiling is reached before a current threshold is reached.

165. The computer-implemented method according to claim 1, further comprising terminating the steady series when a total pulse count including the dynamic series and the steady series reaches a preset total pulse count.

166. The computer-implemented method according to claim 1, further comprising synchronizing application of the electroporation pulses to a heartbeat of a subject.

167. The computer-implemented method according to claim 1, wherein each electroporation pulse has a duration of 90 to 110 microseconds.

168. A control unit for controlling application of electroporation pulses between a proximal electrode assembly and a distal electrode assembly, the control unit comprising:a processor; anda memory storing instructions that, when executed by the processor, cause the control unit to:establish a voltage ceiling for a pulse application routine;drive a dynamic series of electroporation pulses between the proximal electrode assembly and the distal electrode assembly;measure a current associated with the dynamic series;adjust a voltage of the dynamic series according to the measured current while the voltage remains subject to the voltage ceiling;identify a steady voltage based on the dynamic series; anddrive a steady series of electroporation pulses between the proximal electrode assembly and the distal electrode assembly at the steady voltage.SNP1010-W001169. A control unit for controlling application of electroporation pulses between a proximal electrode assembly and a distal electrode assembly, the control unit comprising:a processor; anda memory storing instructions that, when executed by the processor, cause the control unit to:establish a voltage ceiling for a pulse application routine;drive a dynamic series of electroporation pulses between the proximal electrode assembly and the distal electrode assembly;measure a current associated with the dynamic series;adjust a voltage of the dynamic series according to the measured current while the voltage remains subject to the voltage ceiling;identify a steady voltage based on the dynamic series; anddrive a steady series of electroporation pulses between the proximal electrode assembly and the distal electrode assembly at the steady voltage.

170. The control unit according to claim 103, wherein establishing the voltage ceiling comprises determining the voltage ceiling responsively to an interelectrode distance value indicative of an interelectrode distance.

171. The control unit according to claim 103, wherein establishing the voltage ceiling comprises determining the voltage ceiling responsively to tool data indicative of an identity, a model, or a characteristic of a tool.

172. The control unit according to claim 103, wherein establishing the voltage ceiling comprises determining the voltage ceiling responsively to tissue data indicative of a dimension, a shape, an electrical characteristic, or a biological characteristic of tissue.

173. The control unit according to claim 103, wherein adjusting the voltage of the dynamic series comprises increasing a voltage of a successive electroporation pulse when the measured current is below a current threshold.

174. The control unit according to claim 103, wherein adjusting the voltage of the dynamic series comprises decreasing a voltage of a successive electroporation pulse when the measured current is above a current threshold.

175. The control unit according to claim 103, wherein identifying the steady voltage comprises defining as the steady voltage a voltage of a pulse whose current reaches a current threshold.SNP1010-W001176. The control unit according to claim 103, wherein identifying the steady voltage comprises defining as the steady voltage the voltage ceiling when the voltage ceiling is reached before a current threshold is reached.

177. The control unit according to claim 103, wherein the instructions, when executed by the processor, further cause the control unit to terminate the steady series when a total pulse count including the dynamic series and the steady series reaches a preset total pulse count.

178. The control unit according to claim 103, wherein the instructions, when executed by the processor, further cause the control unit to synchronize application of the electroporation pulses to a heartbeat of a subject.

179. The control unit according to claim 103, wherein each electroporation pulse has a duration of 90 to 110 microseconds.

180. A method for treating a tumor in a subject using electroporation, the method comprising:advancing a distal region of a tool into the subject;positioning a first shaft of the tool such that a first electrode and a second electrode disposed on the first shaft straddle a proximal boundary of the tumor;advancing a second shaft of the tool distally out of the first shaft to form, within the tumor, an initial interelectrode distance between the second electrode and a third electrode disposed on the second shaft;driving, using a control unit electrically coupled to the tool, a first set of electroporation pulses between a first electrode assembly disposed on the first shaft and a second electrode assembly disposed on the second shaft at the initial interelectrode distance;further advancing the second shaft distally out of the first shaft to increase the interelectrode distance to an increased interelectrode distance; anddriving a second set of electroporation pulses between the first electrode assembly and the second electrode assembly at the increased interelectrode distance.

181. The method according to claim 180, wherein the initial interelectrode distance is a minimum recommended distance for application of the electroporation pulses between the first electrode assembly and the second electrode assembly.SNP1010-W001182. The method according to claim 181, wherein the minimum recommended distance is selected based on an axial length of at least one electrode of the first electrode assembly or an axial length of at least one electrode of the second electrode assembly.

183. The method according to claim 182, wherein the axial length is 4 mm and the minimum recommended distance is 1 mm.

184. The method according to claim 182, wherein the axial length is 7 mm and the minimum recommended distance is 2 mm.

185. The method according to claim 182, wherein the axial length is 10 mm and the minimum recommended distance is 3 mm.

186. The method according to claim 180, further comprising, after driving the second set of electroporation pulses, further advancing the second shaft distally out of the first shaft to define a further increased interelectrode distance and driving a third set of electroporation pulses between the first electrode assembly and the second electrode assembly at the further increased interelectrode distance.

187. The method according to claim 186, wherein positioning comprises using bioimpedance sensing to facilitate positioning of electrodes of the first electrode assembly at the proximal boundary of the tumor and positioning of electrodes of the second electrode assembly at a distal boundary of the tumor.

188. Apparatus for use with tissue of a subject, the apparatus comprising a tool that comprises:at a proximal region of the tool, at least one electrical terminal;a set of wires extending from the at least one electrical terminal to a distal region of the tool;a first shaft having a first electrode assembly that includes a first radiopaque electrode and a second radiopaque electrode mounted at a fixed position relative to the first radiopaque electrode such that the first shaft defines a radiolucent window between the first radiopaque electrode and the second radiopaque electrode; anda second shaft having a second electrode assembly that includes a radiopaque tubular structure, an insulator covering a proximal portion of the radiopaque tubular structure but not a distal portion of the radiopaque tubular structure such that the distal portion defines a third electrode and the proximal portion defines a conductor portion, and a fourth electrodeSNP1010-W001mounted at a fixed position relative to the third electrode, the conductor portion extending proximally beyond the fourth electrode,wherein the second shaft is telescopically extendible distally out of the first shaft in a manner that axially moves the second electrode assembly with respect to the first electrode assembly, andwherein the radiopaque tubular structure has an axial length that facilitates fluoroscopically guided axial movement of the second shaft with respect to the first shaft to attain a predefined axial distance between the first electrode assembly and the second electrode assembly by, at the predefined axial distance, a proximal end of the conductor portion being fluoroscopically visible in the radiolucent window.

189. The apparatus according to claim 188, wherein the first shaft is radiolucent at a region between the first radiopaque electrode and the second radiopaque electrode so as to define the radiolucent window.

190. The apparatus according to claim 188, wherein the third electrode is electrically connected to the at least one electrical terminal by the conductor portion being connected to a wire of the set of wires.

191. The apparatus according to claim 188, wherein the apparatus is configured such that, prior to attaining the predefined axial distance, the conductor portion spans the radiolucent window to define a fluoroscopically discernable bridge between the first radiopaque electrode and the second radiopaque electrode.

192. The apparatus according to claim 188, wherein the apparatus is configured such that, upon attaining the predefined axial distance, the radiopaque tubular structure vacates at least part of the radiolucent window to define a fluoroscopically discernable gap within the radiolucent window.

193. The apparatus according to claim 188, wherein the third electrode is more radiopaque than an electrode of the first electrode assembly.

194. The apparatus according to claim 188, wherein the apparatus is configured such that a known axial length and radiopacity of the third electrode are usable for interpreting a fluoroscopy image by correcting geometric distortion or determining an angle of the second shaft with respect to a fluoroscope.SNP1010-W001195. A method for fluoroscopically guided positioning of electrodes of a tool for electroporation of a tumor in a subject, the method comprising:advancing a first shaft of the tool into the subject, the first shaft carrying a first electrode assembly that includes a first radiopaque electrode and a second radiopaque electrode at a fixed position relative to the first radiopaque electrode such that the first shaft defines a radiolucent window between the first radiopaque electrode and the second radiopaque electrode;advancing a second shaft of the tool distally relative to the first shaft, the second shaft carrying a second electrode assembly that includes a radiopaque tubular structure having an insulated proximal conductor portion and an uncovered distal portion that defines an electrode;fluoroscopically observing the radiolucent window while advancing the second shaft relative to the first shaft;identifying attainment of a predefined interelectrode distance based on a fluoroscopic position of a proximal end of the proximal conductor portion relative to the radiolucent window; andresponsive to identifying attainment of the predefined interelectrode distance, driving electroporation pulses between electrodes of the tool.

196. The method according to claim 195, wherein fluoroscopically observing comprises observing the proximal conductor portion spanning the radiolucent window as a bridge prior to attaining the predefined interelectrode distance.

197. The method according to claim 195, wherein identifying attainment comprises identifying that the proximal end of the proximal conductor portion is disposed within the radiolucent window.

198. The method according to claim 195, wherein identifying attainment comprises identifying complete absence of the radiopaque tubular structure within the radiolucent window.

199. The method according to claim 195, further comprising utilizing a known axial length and radiopacity of the electrode defined by the uncovered distal portion of the radiopaque tubular structure to interpret a fluoroscopy image.

200. The method according to claim 195, wherein the electrode defined by the uncovered distal portion of the radiopaque tubular structure is more radiopaque than an electrode of theSNP1010-W001first electrode assembly, thereby facilitating viewing of the electrode defined by the uncovered distal portion through the electrode of the first electrode assembly.

201. The method according to claim 195, wherein the predefined interelectrode distance is a minimum recommended distance for application of the electroporation pulses between electrode assemblies in order to reduce a chance of arcing.

202. A method for treating a tumor in a subject using electroporation, the method comprising:advancing a first shaft of a tool into the tumor such that a first electrode assembly carried by the first shaft is positioned with electrodes of the first electrode assembly straddling a proximal boundary of the tumor;advancing a second shaft of the tool distally relative to the first shaft such that a second electrode assembly carried by the second shaft is positioned within the tumor at a first interelectrode distance from the first electrode assembly;driving a first set of electroporation pulses between the first electrode assembly and the second electrode assembly at the first interelectrode distance;further advancing the second shaft distally relative to the first shaft such that the second electrode assembly is repositioned within the tumor at a second interelectrode distance greater than the first interelectrode distance; anddriving a second set of electroporation pulses between the first electrode assembly and the second electrode assembly at the second interelectrode distance.

203. A method for treating a tumor in a subject using electroporation, the method comprising:advancing a first shaft of a tool into the tumor such that a first electrode assembly carried by the first shaft is positioned with electrodes of the first electrode assembly straddling a proximal boundary of the tumor;advancing a second shaft of the tool distally relative to the first shaft such that a second electrode assembly carried by the second shaft is positioned within the tumor at a first interelectrode distance from the first electrode assembly;driving a first set of electroporation pulses between the first electrode assembly and the second electrode assembly at the first interelectrode distance;SNP1010-W001further advancing the second shaft distally relative to the first shaft such that the second electrode assembly is repositioned within the tumor at a second interelectrode distance greater than the first interelectrode distance; anddriving a second set of electroporation pulses between the first electrode assembly and the second electrode assembly at the second interelectrode distance.

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