Systems and devices for treating lung tumors

Abstract

A system for treating a target site of pulmonary tissue includes a flow regulator configured to be interposed between a conductive fluid source and a conductive fluid outlet at a distal portion of a catheter to be positioned at the target site, the conductive fluid outlet being positionable at or near the target site of pulmonary tissue, the flow regulator further configured to control the flow rate or bolus of conductive fluid from the fluid source and delivered to the target site through the conductive fluid outlet, an ablation electrode attached to the distal portion of the catheter, and a controller configured to control the flow regulator and configured to control power delivered from the ablation energy source to the ablation electrode, the controller configured to control a control parameter. and a controller configured to receive one or more values ​​of the data, control the transfer of power from the ablation energy source to the ablation electrode while power is transferred to the ablation electrode, control the flow regulator to maintain a temperature at the target site within a first temperature range by adjusting the flow of conductive fluid delivered to the conductive fluid outlet, determine an amount of conductive fluid to be delivered to the conductive fluid outlet, and in response to the amount of conductive fluid reaching a threshold amount, discontinue the flow of conductive fluid to the conductive fluid outlet, and maintain a temperature at the target site within a second temperature range by adjusting the power delivered to the ablation electrode during discontinuation of the flow of conductive fluid to the conductive fluid outlet.

Description

Detailed description of the invention

[0001] [Related applications] This application claims priority under U.S. Provisional Application 63 / 071,805, filed on 28 August 2020, and is invoked by reference to that application in its entirety.

[0002] [Technical field] This disclosure generally pertains to devices and methods for ablating malignant lung tumors, and more specifically to ablating lung tumors via an approach through the patient's airway.

[0003] [background] Lung cancer remains the leading cause of cancer-related death worldwide. In fact, lung cancer accounts for more deaths annually in this country than breast cancer, colon cancer, and prostate cancer combined. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and it is named after the type of cells inside the lung in which the cancer develops. Approximately 75-80% of lung cancer patients have NSCLC. Early-stage NSCLC refers to cancer that has not spread extensively outside the primary tumor. The earlier lung cancer is detected and treated, the better the outcome. The current standard of treatment for early-stage lung cancer consists of surgical resection of as much of the cancer as possible, followed by chemotherapy and / or radiation therapy.

[0004] Surgical resection of the lung or lobe is the gold standard treatment for stage 1 or 2 non-small cell lung cancer (NSCLC). Unfortunately, only about 15% to 30% of patients diagnosed with lung cancer each year are candidates for surgery. In particular, many patients with concomitant chronic obstructive pulmonary disease (COPD) are not considered suitable candidates for surgery.

[0005] Percutaneous radiofrequency ablation (RFA), using needle electrodes inserted through the chest wall under CT guidance, is increasingly being adopted as a treatment option for primary and metastatic lung tumors. The immediate procedural success rate exceeds 95%, perioperative mortality is low, and the incidence of major complications is 8–12%. Although pneumothorax is the most common complication, fewer than 10% of cases require chest drainage. Sustained complete remission of the tumor has been reported in 85–90% of target lesions.

[0006] Bronchial ablation of lung tumors has been recognized by many as the next frontier in non-surgical thermal tumor ablation, but has been held back by the lack of specialized equipment to generate a sufficient volume of damaged tissue at the target site. This limitation is further complicated by the need to operate through the working channel of the bronchoscope, the difficulty of endoscopically navigating the ablation electrode to the target tumor, and the unique properties of lung tissue, such as being well perfused by blood flow, cooled by perfusion, evaporation, and convection, taking in a large amount of air that can increase the electrical impedance of the RF transmission path and deform the volume of the target tissue in sync with respiration. Since microwave energy propagates well through air, considering the latter, the preference trend of research is steered toward microwave energy. However, RF heating of tissues evaluated in this field has the advantages of simplicity and efficiency.

[0007] From the above perspective, the need remains for improvements in RF energy delivery methods and devices to demonstrate their suitability for bronchoscopy-induced ablation of lung tumors. To reach tumors close to the periphery of the lung, it is even more desirable that the device be flexible, relatively pliable, and fit into a working channel with a small diameter, preferably less than 2 mm.

[0008] [overview] This disclosure relates to a method, apparatus, and system for transbronchial ablation of lung tumors. Aspects of this disclosure include:

[0009] Apparatus and system suitable for delivering a conductive fluid (e.g., HTS) to the airway through an intrabronchial ablation catheter in order to reduce tissue impedance and increase the effective RF energy transfer electrode size,

[0010] Obstructing the airway leading to the target tumor,

[0011] Ablation electrodes are used to surround or penetrate the tumor, peripherally or centrally.

[0012] Ablation of tumors with RF ablation energy using monopolar, multiple monopolar, bipolar, multipolar, and multiphase RF configurations,

[0013] The procedure involves ablating the tumor with RF ablation energy, perfusing the RF electrode with physiological saline or hypertonic saline, or other biocompatible conductive solution (e.g., calcium chloride, magnesium chloride, sodium carbonate, sodium chloride, sodium citrate, sodium hydroxide, or sodium nitrate), and controlling the RF ablation energy using feedback from a temperature sensor, the salinity of the perfusion, temperature, flow rate, or impedance.

[0014] To ablate a tumor, the portion of the lung containing the tumor is to collapse, compress, reduce the air volume, or partially collapse.

[0015] The ablation catheter is positioned via a guidewire, and the bronchoscope is replaced.

[0016] Using over-the-wire exchange of the bronchoscope and electrode catheter, the placement of electrodes within the airway,

[0017] Placement of a needle electrode into a tumor using a spring-loaded or push-pull catheter handle design,

[0018] Based on the positive biopsy result at the site, the guided biopsy tool will be replaced with a non-guided or guided ablation tool, and moved to the same biopsy site under the guidance of fluorescence fluoroscopy or ultrasound.

[0019] This includes reducing oxygen in the aforementioned site and causing localized hypoxic vasoconstriction, thereby reducing blood flow to the target site in the lung, either before or during the transfer of ablation energy.

[0020] Intrabronchial navigation uses CT image data to create a navigation plan that facilitates the advancement of the ablation catheter through the bronchoscope and the patient's bronchial branching toward the nodule. Electromagnetic tracking may also be used in conjunction with CT data to facilitate the guidance of the ablation catheter through the bronchial branching toward the nodule. The ablation catheter may be positioned within one of the airways of a branched lumen network, near or within the nodule or point of interest. Once positioned, fluoroscopy may be used to visualize the ablation catheter as it moves further toward the nodule or point of interest. Other imaging techniques, such as MRI and ultrasound, may be used in combination with or instead of fluoroscopy or CT in conjunction with navigation bronchoscopy. If necessary, the intrabronchial ablation catheter may be fitted with sensors (e.g., 3D electromagnet coils, fiber Bragg grating sensors, etc.) that are compatible with the navigation bronchoscopy system available in the field.

[0021] One or more aspects of the present invention are disclosed below.

[0022] The first aspect relates to a system for treating a target site in lung tissue, the system comprising at least one flow regulator configured to be interposed between a conductive fluid source and a conductive fluid outlet that can be placed at or near the target site in the lung tissue, the flow regulator being further configured to control the flow rate or bolus dose of the conductive fluid exiting the fluid source and delivered to the conductive fluid outlet, a controller communicably connected to the flow regulator and at least one sensor, the at least one sensor being configured to detect a value taken by at least one control parameter representing a physical property, the physical property being one of temperature (T), pressure (p), electrical impedance (Z), or conductivity (C) of a substance present at or near the target site in the lung tissue, wherein the controller - receives from the sensor a signal representing the value of the detected control parameter, - controls the flow regulator based on the value of one or more detected control parameters, is configured as such, Controlling the flow regulator comprises o controlling the flow regulator in a high delivery mode, in which mode ■ the flow rate of the conductive fluid delivered to the conductive fluid outlet is greater than or equal to a set high flow rate, or ■ the bolus dose of the conductive fluid delivered to the conductive fluid outlet is greater than or equal to a set high bolus dose, controlling in the high delivery mode and o controlling the flow regulator in a low delivery mode, in which mode ■ the flow rate of the conductive fluid delivered to the conductive fluid outlet is less than or equal to a set low flow rate less than the set high flow rate, or, ■ the bolus dose of the conductive fluid delivered to the conductive fluid outlet is less than or equal to a set low bolus dose less than the set high bolus dose, controlling in the low delivery mode and including executing a control cycle including the above.

[0023] A second embodiment according to the first embodiment, wherein in the low delivery mode, the flow rate of the conductive fluid delivered to the conductive fluid outlet is less than or equal to a set low flow rate, which is less than 50% of the set high flow rate, or the bolus dose of the conductive fluid delivered to the conductive fluid outlet is less than or equal to a set low bolus dose, which is less than 50% of the set high bolus dose.

[0024] A third embodiment according to the first or second embodiment, wherein in the low delivery mode, the set low flow rate is 0 to 5 ml / min, or the set low bolus dose is 0 to 10 ml.

[0025] A fourth embodiment according to the first, second, or third, wherein in high-delivery mode, the set high flow rate is 2 to 16 ml / min, or the set high bolus dose is 0.3 to 60 ml.

[0026] A fifth embodiment, which is one of the first to fourth embodiments, wherein controlling the flow regulator includes repeatedly executing the above control cycle.

[0027] A sixth embodiment, according to any one of the first to fifth embodiments, comprises at least one ablation element that can be positioned at a target site in lung tissue and can be connected to an ablation source.

[0028] A seventh aspect according to the sixth aspect comprises at least one flexible shaft having an active portion that is configured to advance through the airway passages of the lung and can be positioned at a target site in the lung tissue, and includes at least one ablation element.

[0029] An eighth embodiment, based on any one of the preceding first to seventh embodiments, comprises at least one sensor, which is configured to be positioned at a target site in lung tissue.

[0030] A ninth embodiment according to a seventh embodiment, which is combined with any one of embodiments 1 to 6 and 8, wherein at least one sensor is carried by the active portion of the flexible shaft.

[0031] A tenth embodiment according to a seventh embodiment, which is combined with any one of embodiments 1 to 6 and 8, wherein at least one sensor is configured to be positioned corresponding to the volume surrounding the active portion of the flexible shaft.

[0032] An eleventh embodiment according to embodiment 9 or 10, wherein at least one sensor is configured to detect a value taken by at least one control parameter, the physical property being one of the temperature, pressure, electrical impedance, or conductivity of a substance present in the volume surrounding the active part.

[0033] A twelfth embodiment according to any one of the preceding embodiments includes a conductive fluid outlet configured to be installed in fluid communication with a conductive fluid source.

[0034] A thirteenth embodiment according to embodiments 7 and 12, wherein the conductive fluid outlet is carried by the active portion of the flexible shaft.

[0035] A fourteenth embodiment according to embodiments 7 and 12, wherein the conductive fluid outlet is configured to be positioned in accordance with the volume surrounding the active portion.

[0036] A fifteenth embodiment according to any one of the preceding embodiments 6 to 14, wherein the controller is connectable to the ablation source and is configured to control the ablation energy source to transfer ablation energy to at least one ablation element.

[0037] A 16th aspect according to the 15th aspect, wherein the controller is configured to perform the steps of: receiving a signal from the sensor representing a value of a detected control parameter; controlling a flow regulator based on the value of one or more detected control parameters; and performing the control cycle, which may be repeated as needed, while the controller commands an ablation energy source to deliver ablation energy to at least one ablation element.

[0038] A 17th embodiment, according to any one of the preceding embodiments 7 to 16, comprises an electrical connector that is carried by a flexible shaft and configured to electrically connect at least one ablation element to an ablation source.

[0039] An 18th embodiment according to any one of the preceding embodiments, wherein the control cycle includes checking whether the value of one or more detected control parameters falls below a set low threshold (T_Low), and controlling the flow regulator to low delivery mode is performed if the value of one or more detected control parameters falls below a set low threshold (T_Low).

[0040] A 19th embodiment according to any one of the preceding embodiments, wherein the control cycle includes checking whether the value of one or more detected control parameters exceeds a set high threshold (T_High, Z_High), and controlling the flow regulator to high-delivery mode is performed if the value of the detected control parameters exceeds the set high threshold (T_High, Z_High).

[0041] A 20th embodiment of any one of the preceding embodiments, wherein the control cycle includes periodically checking whether the value of one or more detected control parameters falls below a set low threshold (T_Low), and switching the flow regulator from high-delivery mode to low-delivery mode when the value of one or more detected control parameters falls below the set low threshold (T_Low), wherein the periodic checking step is performed at least 10 times per second, if necessary.

[0042] A 21st embodiment according to any one of the preceding embodiments, wherein the control cycle includes periodically checking whether the value of one or more detected control parameters exceeds a set high threshold (T_High, Z_High), and switching the flow regulator from a low delivery mode to a high delivery mode when the value of one or more detected control parameters exceeds a set high threshold (T_High, Z_High), wherein the periodic checking step is performed at least 10 times per second, if necessary.

[0043] A 22nd embodiment according to any one of the preceding embodiments, wherein the controller is configured to repeat control cycles multiple times during the same treatment session.

[0044] A 23rd embodiment according to embodiment 22, wherein the controller is configured to control the flow regulator in high-delivery mode or low-delivery mode for the duration of each time interval, the duration of each time interval being predetermined or determined by the detection of a trigger event.

[0045] A 24th aspect according to aspect 23, wherein the controller is configured to determine the duration of the time interval by detecting a trigger event, and the detection of the trigger event is - Detection of one or more detected parameter values ​​exceeding the set ultra-high threshold (T_Overheat), - Detection of the value of one or more detected parameters exceeding the above set high threshold (T_High, Z_High), - Detection of one or more detected parameter values ​​falling below the set low threshold (T_Low), Includes one or more of the following.

[0046] A 25th embodiment according to embodiment 22, 23, or 24, wherein the controller is configured to perform the same treatment session comprising a plurality of time intervals in which the flow regulator is adjusted to a low delivery mode, interspersed with a time interval in which the flow regulator is adjusted to a high delivery mode, thereby reducing the total amount of conductive fluid delivered over the treatment session while maintaining control over the value of the detected parameter.

[0047] A 26th embodiment according to any one of the preceding embodiments, wherein the step of controlling the flow regulator to a low delivery mode includes adjusting the flow regulator to maintain the flow rate of conductive fluid to the conductive fluid outlet at or below the set low flow rate, particularly during a low delivery time interval (Flow Low Time) which includes 1 to 10 seconds, or adjusting the flow regulator to deliver a bolus dose of conductive fluid to the conductive outlet at or below the set low bolus dose, particularly during a low delivery time interval (Flow Low Time) which includes 1 to 10 seconds.

[0048] A 27th aspect according to aspect 26, wherein the cycle includes a subroutine that is executed as necessary after the end of the low delivery time interval, the subroutine is - A further step is to check whether the value of one or more detected parameters is below or above the set low threshold (T_Low), -In the further verification step, if the value of one or more detected parameters falls below the set low threshold (T_Low), the reduced value is specified as the set low flow rate or set low bolus dose. - Repeatedly controlling the flow regulator to low delivery mode using a reduced value for the set low flow rate or a reduced value for the set low bolus dose, Includes.

[0049] A 28th embodiment according to any one of the preceding embodiments, wherein the step of controlling the flow regulator to a high-delivery mode is: - In particular, during the high-delivery time interval (Flow High Time) included in 1 to 30 seconds, adjust the flow regulator to maintain the flow rate of conductive fluid to the conductive fluid outlet at or above the set high flow rate, or - In particular, during the high delivery time interval (Flow High Time) which is included in 1 to 30 seconds, adjust the flow regulator so that a bolus dose of conductive fluid is delivered to the conductive fluid outlet at or above the set high bolus dose. Includes.

[0050] A 29th aspect according to aspect 28, wherein the cycle includes a subroutine that is executed as necessary after the end of the high delivery time interval, the subroutine is - A further step is to check whether the value of one or more detected parameters is below or above the set low threshold (T_Low), -In the further verification step, if the value of one or more detected parameters remains above the set low threshold (T_Low), the increased value is specified as the set high flow rate or set high bolus dose. - Repeatedly controlling the flow regulator to high-delivery mode using an increased value for the set high flow rate or an increased value for the set high bolus dose, Includes.

[0051] A 30th aspect according to aspect 29, wherein the cycle is repeated until a further step of checking whether one or more detected values ​​fall below a set low threshold (T_Low) is positively passed.

[0052] A 31st embodiment according to embodiments 16 and 30, wherein the controller is configured to stop or reduce the transfer of ablation energy to at least one ablation element if it is determined that, after a predetermined number of repetitions of the subroutine of embodiment 29, the step of checking whether one or more detected values ​​fall below a set low threshold (T_Low) is not positively passed.

[0053] A 32nd aspect, which is any one of the preceding aspects, wherein the cycle is - If the value of one or more parameters exceeds a set ultra-high threshold (T_Over High, Z_Over High) which is greater than the above high threshold (T_High, Z_High), then it is determined that a safety-related event has occurred. -When a safety-related condition is determined, 〇Temporarily reduce the power supplied to the ablation energy source, and / or The flow regulator is controlled to the ultra-high delivery mode, and in the ultra-high delivery mode, the flow rate of conductive fluid delivered to the conductive fluid outlet is greater than or equal to the set ultra-high flow rate, which is greater than the set high flow rate, or the bolus dose of conductive fluid delivered to the conductive fluid outlet is greater than or equal to the set ultra-high bolus dose, which is greater than the high bolus dose.

[0054] A 33rd embodiment, relating to any one of the preceding embodiments 6 to 32, wherein the controller is configured to maintain the power supplied by the ablation energy source within the range of 20 to 200 W over the main part of the treatment session, and, if necessary, over the entire treatment session.

[0055] A 34th embodiment, which is one of the preceding embodiments 6 to 33, wherein the controller is configured to increase the power supplied by the ablation energy source from an initial value to a regimen value during the initial part of the treatment session and, if necessary, for 10% to 30% of the entire treatment session.

[0056] A 35th embodiment according to embodiment 34, wherein the controller is configured to maintain the power supplied by the ablation energy source at a regimen value during the main part of the treatment session following the initial part of the treatment session.

[0057] A 36th aspect according to aspect 35, wherein the initial value is included in 20W to 80W, the regimen value is included in 40W to 200W, and furthermore, the initial value is less than 80% of the regimen value, and if necessary, less than 50% of the regimen value.

[0058] A 37th embodiment, which is one of the preceding embodiments 22 to 36, wherein the treatment session has a total treatment duration that is included in 30 seconds to 30 minutes.

[0059] A 38th embodiment, relating to any one of the preceding embodiments 6 to 37, wherein the controller is configured to automatically instruct the flow regulator to automatically stop the transmission of power from the ablation energy source and to stop the delivery of conductive fluid when the treatment duration is finished.

[0060] A 39th embodiment according to any one of the preceding embodiments 22 to 38, wherein the controller is configured to control a flow regulator so that the maximum amount of conductive fluid delivered during a treatment session is between 0.3 ml and 60 ml and / or the average flow rate of conductive fluid maintained during a treatment session is between 0.1 and 15 ml / min, in particular the controller is configured to automatically stop the transmission of power from the ablation energy source and / or to automatically instruct the flow regulator to stop the delivery of conductive fluid when the maximum amount of conductive fluid to be delivered is reached.

[0061] A 40th embodiment, which is one of the preceding embodiments 1 to 39 combined with one of embodiments 18 to 21, wherein the set high threshold (T_High) is greater than the set low threshold (T_Low).

[0062] A 41st aspect, which is a combination of aspect 24 and aspect 40, wherein the set ultra-high threshold (T_Overheat) is greater than the set high threshold (T_High).

[0063] A 42nd embodiment according to any one of the preceding embodiments, wherein the physical property is the temperature of the substance present in the target area, and in particular, when this embodiment also corresponds to embodiment 11, the physical property is the temperature of the substance present in the volume surrounding the active part.

[0064] A 43rd embodiment according to embodiments 40 and 42, wherein the set low threshold (T_Low) is 60 to 95°C.

[0065] A 44th embodiment according to embodiment 40, which is combined with one of embodiment 42 or 43, wherein the set high threshold (T_High) is from more than 75°C to 105°C.

[0066] A 45th embodiment according to embodiment 41, which is combined with one of embodiment 42, 43, or 44, wherein the set ultra-high threshold (T_Overheat) is 85 to 115°C.

[0067] A 46th embodiment according to any one of the preceding embodiments 1 to 45, wherein the ablation energy source is a radio frequency generator, and the controller is configured to control the radio frequency generator to transmit RF having a power in the range of 1 to 200 W, particularly in the range of 20 to 200 W, for a duration of 30 seconds to 30 minutes.

[0068] A 47th embodiment according to any one of the preceding embodiments 1 to 46, wherein the flow regulator comprises a pump, optionally a syringe pump or peristaltic pump, or an injection pump or valve.

[0069] A 48th embodiment, according to any one of the preceding embodiments 7 to 47, comprises a conductive fluid source configured to deliver a hypertonic saline solution, and a fluid port connectable to the conductive fluid source and in fluid communication with a conductive fluid outlet, wherein the hypertonic saline solution optionally contains a reverse-phase transition polymer and water, and can change to a higher viscosity when transitioning from a temperature below body temperature to body temperature.

[0070] A 49th aspect according to aspect 48, wherein the hypertonic saline solution contains one or more physiologically acceptable solutes and has a theoretical osmolality of 0.8 to 15 Osm / L calculated by the following formula,

number

[0071] A 50th aspect according to aspect 48 or 49, wherein the hypertonic saline solution contains sodium chloride (NaCl) at a concentration of 3% to 30% (w / v).

[0072] A 51st embodiment according to any one of the preceding embodiments 7 to 50, wherein the flexible shaft is a flexible shaft of an ablation catheter.

[0073] A 52nd aspect according to aspect 51, wherein the ablation catheter has a fluid port located at the proximal end of the flexible shaft and in fluid communication with a conductive fluid outlet located in the active portion of the flexible shaft.

[0074] A 53rd embodiment according to any one of the preceding embodiments 7 to 52, wherein the active part is the distal end of the flexible shaft.

[0075] A 54th embodiment, according to any one of the preceding embodiments 7 to 53, comprises at least one space closure plug that is operable in or near the active portion of the flexible shaft, particularly at or near the distal end of the flexible shaft.

[0076] A 55th aspect according to aspect 54, wherein the space closure plug is one of a tapered shaft, a deployable balloon, a deployable valve, or a deployable stent.

[0077] A 56th embodiment according to embodiment 54 or 55, wherein the occlusion plug includes a deployable occlusion balloon having a first cross-section with a width of 1 to 30 mm and a length in the range of 5 to 30 mm, the occlusion balloon being configured to expand to occlude a portion of the airway.

[0078] A 57th aspect according to aspect 56, wherein the first cross-sectional width is located in the proximal part of the deployable occluded balloon, the second cross-sectional width in the range of 1 to 30 mm is located in the distal part of the balloon, and the cross-sectional width between the first and second cross-sectional widths is smaller than both of the first and second cross-sectional widths.

[0079] A 58th aspect according to aspect 56, wherein the first cross-sectional width is located in the proximal part of the deployable occluding balloon, and the second cross-sectional width, which is smaller than the first cross-sectional width in the range of 1 to 20 mm, is located in the distal part of the balloon.

[0080] A 59th embodiment, according to any one of the preceding embodiments 7 to 58, comprises a tubular sheath or bronchoscope for receiving the flexible shaft, wherein at least the active portion of the flexible shaft, particularly the distal end, is configured to emerge from the tubular sheath or bronchoscope.

[0081] A 60th embodiment according to embodiment 59, which is combined with any one of embodiments 54 to 58, wherein the space closure plug is carried by a tubular sheath or a bronchoscope.

[0082] A 61st embodiment according to any one of embodiments 54 to 58, wherein at least one space closure plug is carried directly by a flexible shaft or by another shaft.

[0083] A 62nd embodiment, according to any one of embodiments 54 to 61, further comprises an inflatable lumen extending through a flexible shaft and having a proximal end connectable to a fluid source, optionally a liquid source or a gas source, and a distal end in fluid communication with the inside of a balloon.

[0084] A 63rd embodiment, which is one of the preceding embodiments 7 to 62, wherein the flexible shaft has depth markers at least 5 cm in the proximal portion and 5 cm in the distal portion.

[0085] A 64th embodiment, according to any one of the preceding embodiments 7 to 62, has at least one suction port at the distal end of a flexible shaft, configured to be installed in fluid communication with a vacuum source in order to draw air from a lung volume surrounding the distal end of the shaft.

[0086] A 65th embodiment according to embodiment 64, which is combined with any one of embodiments 54 to 63, wherein at least one suction port is positioned distal to the space seal.

[0087] A 66th aspect according to aspect 64, which is combined with any one of aspects 54 to 63, comprises an additional space closure plug that is operable at or near the distal end of the shaft, in particular the additional space closure plug being one of a deployable balloon, a deployable valve, or a deployable stent, and at least one suction port being located between the space closure plug and the additional space closure plug.

[0088] A 67th aspect according to aspect 65 or 66, wherein at least one conductive fluid outlet is located distal to the space seal or between the space seal and an additional space seal.

[0089] A 68th embodiment according to any one of embodiments 54 to 67, wherein at least one sensor is positioned distal to the space seal or between the space seal and an additional space seal.

[0090] A 69th aspect according to aspect 67, wherein at least one sensor is carried by the distal end of a flexible shaft, and the physical property is one of the temperature, pressure, electrical impedance, or conductivity of a material surrounding the distal end of the flexible shaft.

[0091] A 70th embodiment according to embodiment 68 or 69, wherein at least one sensor includes a first sensor positioned proximal to the ablation element and a second sensor positioned distal to the ablation element.

[0092] A 71st embodiment according to any one of the preceding embodiments 7 to 70, wherein at least one ablation element includes an ablation element having a rounded distal end that is positioned at the distal end of a flexible shaft.

[0093] A 72nd aspect according to aspect 64, which can be combined with any of aspects 54-63 and 65-71, comprises a common lumen extending through a flexible shaft, having a proximal end selectively connectable to at least one of a conductive fluid source and a vacuum source, and a distal end forming a common opening defining the at least one outlet and the at least one inlet; or a dedicated perfusion lumen and a dedicated air suction lumen, wherein the perfusion lumen is connected to at least one outlet and extends through the catheter flexible shaft, and the perfusion lumen has an injection port configured to be connected to a conductive fluid source; and the air suction lumen is connected to at least one air inlet and extends through the catheter flexible shaft, and the air suction lumen has an inhalation port configured to be connected to a vacuum source.

[0094] A 73rd embodiment according to any one of the preceding embodiments 7 to 72, wherein the flexible shaft has an outer diameter of 2 mm or less.

[0095] A 74th embodiment according to any one of the preceding embodiments 7 to 73, wherein at least a portion of the flexible shaft can be bent such that the curved portion of the shaft has a radius of curvature of at least 7 mm.

[0096] A 75th embodiment, which is one of the preceding embodiments 7 to 74, wherein the flexible shaft has a length of at least 50 cm.

[0097] A 76th embodiment according to any one of the preceding embodiments 7 to 75, wherein the elongated shaft is provided with a guidewire lumen configured to receive a guidewire at its distal end.

[0098] A 77th aspect according to aspects 72 and 76, wherein the suction lumen and the guidewire lumen are formed by a common lumen.

[0099] A 78th embodiment relating to any one of the preceding embodiments 6 to 77, wherein the ablation element has one or more of the following features, 120 mm 2 It includes at least one electrode characterized by the following: total surface area, diameter in the range of 0.5 to 2 mm, and length in the range of 3 to 20 mm.

[0100] A 79th embodiment according to any one of the preceding embodiments 6 to 78, wherein at least one ablation element includes at least two electrodes, and the distance between the electrodes is 5 to 15 mm.

[0101] An 80th embodiment according to any one of the preceding embodiments comprises an interface component that is connectable to the at least one sensor and is at least communicatively connectable to the controller for transmitting the detected value of the at least one control parameter detected by the sensor to the controller.

[0102] An 81st embodiment according to any one of the preceding embodiments, wherein the controller is -Process the detected values ​​above. -Based on one or more of the above detected values, A user-recognizable output, which includes, if necessary, an audible, visual, or vibrational signal to notify the user to deploy at least one space closure plug that can operate at or near the distal end of the shaft, A state output representing the degree of reduction in air volume in the lung area located at the distal end of the catheter. Output command to automatically deploy at least one space closure plug that can operate at or near the distal end of the shaft. 〇Temperature output that provides an indicator of the temperature of the material surrounding the distal end of the flexible shaft, 〇 Electrical characteristic output that provides an indicator of the impedance or conductivity of the material surrounding the distal end of the shaft. 〇 Pressure output that provides an indicator of the pressure of the material surrounding the distal end of the flexible shaft, It is configured to generate at least one output signal that includes one or more of the following:

[0103] An 82nd embodiment according to any one of the preceding embodiments, wherein the controller is A signal is received from at least one sensor, which is a temperature sensor configured to monitor the temperature at the target site, To maintain the temperature value detected by the temperature sensor within a defined temperature range or above a certain temperature threshold, the conductivity or composition of the conductive fluid delivered through the at least one outlet is controlled based on the monitored temperature. It is configured in this way.

[0104] The 83rd system of any one of the preceding embodiments, wherein the controller is A signal is received from at least one sensor, which is a temperature sensor, and in particular, when this embodiment is according to embodiment 7, the sensor is configured to detect a temperature value of a material surrounding the distal end of a flexible shaft, Monitor the temperature of the target site, To maintain the temperature value detected by the temperature sensor within a defined temperature range or above a specific temperature threshold, the ablation energy power output from the energy source is adjusted. It is configured in this way.

[0105] An 84th embodiment according to embodiment 82 or 83, wherein the defined temperature range is 60 to 115°C, and a certain temperature threshold is at least 80°C.

[0106] An 85th embodiment, according to any one of the preceding embodiments 1 to 84, further comprises a navigation sensor, such as a 3D navigation sensor, or a shape sensor, such as a fiber Bragg grating sensor, at least in the distal end region, wherein the navigation sensor is one or more of an electromagnetic sensor, a 3D electromagnetic sensor, a shape sensor, an FBG sensor, a 3D ultrasonic sensor, and an impedance tracking sensor for 3D navigation.

[0107] An 86th embodiment according to any one of the preceding embodiments 7 to 85, further comprising a puncture element at the distal end of a flexible shaft configured to advance through a tumor, wherein the puncture element is selected from a list including a needle, a deployable needle, and an RF puncture electrode.

[0108] An 87th embodiment, which is one of the preceding embodiments 6 to 87 combined with embodiment 54, wherein the distance between the space closure plug and the ablation element is in the range of 1 mm to 40 mm.

[0109] The 88th aspect relating to an ablation catheter is: A flexible shaft configured to advance through the airway passages of the lungs, An ablation element is located at the distal end of a flexible shaft and is electrically connectable to an ablation energy source, A fluid port that can be connected to a conductive fluid source, At least one outlet for a conductive fluid, the outlet located at the distal end and in fluid communication with the fluid port, It is equipped with.

[0110] An 89th aspect according to aspect 88 further comprises at least one space closure plug that is operable at or near the distal end of the shaft, the space closure plug being one of a tapered shaft portion, a deployable balloon, a deployable valve, or a deployable stent.

[0111] A 90th aspect according to aspect 89, wherein the occlusion plug includes a deployable occlusion balloon having a first cross-section with a width of 1 to 30 mm and a length in the range of 5 to 30 mm, the occlusion balloon being configured to expand to occlude a portion of the airway.

[0112] A 91st aspect according to aspect 90, wherein the first cross-sectional width is located in the proximal part of the deployable occluding balloon, the second cross-sectional width in the range of 1 to 30 mm is located in the distal part of the balloon, and the width between the first and second cross-sectional widths is smaller than both of the widths of the first and second cross-sections.

[0113] A 92nd aspect according to aspect 90, wherein a first cross-sectional width is located in the proximal part of the deployable occluding balloon and is in the range of 1 to 20 mm, and a second cross-sectional width smaller than the first cross-sectional width is located in the distal part of the balloon.

[0114] A 93rd embodiment according to embodiments 88 to 92 comprises a tubular sheath or bronchoscope that receives the shaft, wherein at least the distal end of the flexible shaft is configured to emerge from the tubular sheath or bronchoscope.

[0115] A 94th embodiment according to embodiment 93, combined with embodiment 90, wherein the space closure plug is carried by a tubular sheath or a bronchoscope, or at least one space closure plug is carried directly by a shaft or by different shafts.

[0116] A 95th embodiment, in combination with embodiment 90, according to any of embodiments 88 to 94, further comprises an inflatable lumen having a proximal end extending through a flexible shaft and connectable to a fluid source, optionally a liquid source or a gas source, and a distal end in fluid communication with the inside of a balloon.

[0117] A 96th embodiment according to any of embodiments 88 to 95, wherein the flexible shaft has depth markers at least 5 cm in the proximal portion and 5 cm in the distal portion.

[0118] A 97th embodiment according to any of embodiments 88 to 96 has at least one suction port at the distal end of the shaft, configured to be installed in fluid communication with a vacuum source for drawing air from the lung volume surrounding the distal end of the shaft.

[0119] A 98th embodiment according to embodiment 97, which is combined with embodiment 90, wherein at least one suction port is positioned distal to the space seal.

[0120] A 99th aspect according to aspect 98 includes an additional space closure plug that is operable at or near the distal end of the shaft, in particular the additional space closure plug being one of a deployable balloon, a deployable valve, a deployable stent, or a tapered shaft portion, and at least one suction port is located between the space closure plug and the additional space closure plug.

[0121] A 100th embodiment according to any of embodiments 88 to 99, wherein at least one conductive fluid outlet is located distal to the space seal or between the space seal and an additional space seal.

[0122] A 101st embodiment according to any of embodiments 88 to 100 further comprises at least one sensor located distal to the space seal or between the space seal and an additional space seal.

[0123] A 102nd aspect according to aspect 101, wherein at least one sensor is carried by the distal end of a flexible shaft, and the physical property is one of the temperature, pressure, electrical impedance, or conductivity of a material surrounding the distal end of the flexible shaft.

[0124] A 103rd embodiment according to either embodiment 101 or 102, wherein at least one sensor includes a first sensor positioned proximal to the ablation element and a second sensor positioned distal to the ablation element.

[0125] A 104th embodiment according to any of embodiments 88 to 102, wherein at least one ablation element includes an ablation element having a rounded distal end that is positioned at the distal end of a flexible shaft.

[0126] The 105th aspect according to aspect 97, which is combined with any of aspects 88 to 103, is: A common lumen having a proximal end extending through a flexible shaft and selectively connectable to at least one of a conductive liquid source and a vacuum source, and a distal end forming a common opening defining the at least one outlet and the at least one inlet, or A dedicated perfusion lumen and a dedicated air suction lumen, wherein the perfusion lumen is connected to at least one outlet and extends through the catheter shaft, and the perfusion lumen has an injection port configured to be connected to a conductive fluid source, and the air suction lumen is connected to at least one air intake and extends through the catheter shaft, and the air suction lumen has an suction port configured to be connected to a vacuum source, It is equipped with.

[0127] A 106th embodiment according to any of embodiments 88 to 105, wherein the flexible shaft has an outer diameter of less than 2 mm.

[0128] A 107th embodiment according to any of embodiments 88 to 106, wherein at least a portion of the flexible shaft can be bent such that the curved portion of the shaft has a radius of curvature of at least 7 mm.

[0129] A 108th embodiment according to any of embodiments 88 to 107, wherein the flexible shaft has a length of at least 50 cm.

[0130] A 109th embodiment according to any of embodiments 88 to 108, wherein the elongated shaft is provided with a guidewire lumen configured to receive a guidewire at its distal end.

[0131] A 110th embodiment according to either embodiment 105 or 109, wherein the suction lumen and the guidewire lumen are formed by a common lumen.

[0132] An 111th aspect according to any of aspects 88 to 110, wherein the ablation element has one or more of the following features: 120mm 2 The total surface area below, Diameter in the range of 0.5 to 2 mm, Lengths ranging from 3 to 20 mm. It includes at least one electrode characterized by...

[0133] A 112th embodiment according to any of embodiments 88 to 111, wherein at least one ablation element includes at least two electrodes, and the distance between the electrodes is 5 to 15 mm.

[0134] A 113th embodiment, which is combined with embodiment 101 and is one of embodiments 88 to 112, comprises an interface component that is connectable to at least one sensor and is at least communicatively connectable to a controller in order to transmit the value of the at least one control parameter detected by the sensor to the controller.

[0135] A 114th aspect, which is combined with aspect 101, is one of aspects 88 to 113, -Process the detected values ​​above. -Based on one or more of the above detected values, A user-recognizable output, which includes, if necessary, an audible, visual, or vibrational signal to notify the user to deploy at least one space closure plug that can operate at or near the distal end of the shaft, A state output representing the degree of reduction in air volume in the lung region located at the distal end of the flexible shaft. Output command to automatically deploy at least one space closure plug that can operate at or near the distal end of a flexible shaft. 〇Temperature output that provides an indicator of the temperature of the material surrounding the distal end of the flexible shaft, 〇 Electrical characteristic output that provides an indicator of the impedance or conductivity of the material surrounding the distal end of the flexible shaft. 〇 Pressure output that provides an indicator of the pressure of the material surrounding the distal end of the flexible shaft, It includes a controller configured to generate at least one output signal, which includes one or more of the following:

[0136] A 115th embodiment, in combination with embodiment 101, according to any one of embodiments 88 to 114, comprises a controller that receives a signal from at least one sensor, which is a temperature sensor configured to monitor temperature at the target site, and controls the conductivity or composition of a conductive fluid delivered through the at least one outlet based on the monitored temperature in order to maintain the temperature value detected by the temperature sensor within a defined temperature range or above a certain temperature threshold.

[0137] A 116th embodiment according to any one of the preceding embodiments 88 to 115, wherein the controller receives a signal from at least one sensor, which is a temperature sensor, and is configured to detect a temperature value of a material surrounding the distal end of a flexible shaft, particularly when this embodiment is according to embodiment 7, monitors the temperature of a target site, and adjusts the ablation energy power output from an energy source to maintain the temperature value detected by the temperature sensor within a defined temperature range or above a certain temperature threshold.

[0138] A 117th embodiment according to either embodiment 115 or 116, wherein the defined temperature range is 60 to 115°C, and a certain temperature threshold is at least 80°C.

[0139] An 118th embodiment according to any one of the preceding embodiments 88 to 117, further comprising a navigation sensor such as a three-dimensional navigation sensor or a shape sensor such as a fiber Bragg grating sensor in at least the distal end region, wherein the navigation sensor is one or more of an electromagnetic sensor, a 3D electromagnetic sensor, a shape sensor, an FBG sensor, a 3D ultrasonic sensor, and an impedance tracking sensor for 3D navigation.

[0140] A 119th embodiment according to any of embodiments 88 to 118 further comprises a puncture element at the distal end of a flexible shaft configured to advance through a tumor, the puncture element being selected from a list including a needle, a deployable needle, and an RF puncture electrode.

[0141] A 120th embodiment according to any of embodiments 89 to 119, wherein the distance between the space closure plug and the ablation element is in the range of 1 mm to 40 mm.

[0142] A 121st embodiment according to any of embodiments 88 to 120 has a tapered distal end, a lumen that passes through the shaft from the proximal to the distal end, and the lumen exits from the distal end at the narrowest part of the tapered distal end.

[0143] A 122nd aspect of the system comprises the catheter of aspect 121 and a tumor perforation wire configured to advance beyond the distal end through a lumen passing through a shaft from proximal to distal, the tumor perforation wire having a sharp distal end, a depth marker on the proximal end if necessary, and a radiopaque marker on the distal end if necessary.

[0144] A 123rd aspect relating to a solution for the treatment of lung cancer, particularly non-small cell lung cancer (NSCLC), in target sites of the lung airways, -The solution is, It has a theoretical osmolality of 0.8 to 15 Osm / L, calculated by the following formula.

number

[0145] A 124th aspect according to aspect 123, wherein the solution is a hypertonic saline solution.

[0146] A 125th embodiment according to any one of embodiments 123 or 124, wherein the solution has an electrical conductivity that is at least 30 mS / cm, preferably 70 mS / cm to 225 mS / cm, at sea level and 20 degrees.

[0147] A 126th embodiment according to any one of embodiments 123 to 125, wherein the total amount of solution delivered during the total treatment time is contained in 0.3 ml to 60 ml.

[0148] A 127th embodiment according to any one of embodiments 123 to 126, wherein the delivery of the above solution to a target site at a non-constant flow rate includes alternating between low-delivery mode intervals and high-delivery mode intervals, during which the flow rate is maintained at 0 to 10 ml / min or the bolus dose is delivered at 0 to 10 ml, and during which the flow rate is maintained at 2 to 16 ml / min or the bolus dose is delivered at 0.3 to 60 ml.

[0149] A 128th embodiment according to any one of embodiments 123 to 127, wherein delivering the solution to the target site at a non-constant flow rate includes maintaining an average flow rate of the conductive fluid contained in 0.1 to 15 ml / min during the treatment time.

[0150] A 129th embodiment according to any one of embodiments 123 to 128, wherein hypertonic saline is locally delivered to a target site via the airway while RF ablation energy having a power in the range of 1 to 200 W, particularly in the range of 20 to 200 W, is delivered.

[0151] A 130th embodiment according to any one of embodiments 123 to 129, wherein the hypertonic saline solution contains a reverse-phase transition polymer and water, and changes from a lower viscosity to a higher viscosity when transitioning from a temperature below body temperature to body temperature.

[0152] A 131st embodiment according to any one of embodiments 123 to 130, wherein the target site in the lung is isolated by inflating a first occluding balloon in the natural airway leading to the target site, and the solution composition is delivered to the target site while the balloon is proximal to the target site in the lung.

[0153] A 132nd embodiment according to any one of embodiments 123 to 131, wherein the solution is delivered to the target site while the target site of the lung is isolated by inflating the second occluding balloon distal to the first occluding balloon and within the natural airway distal to the target site.

[0154] A 133rd embodiment according to either embodiment 131 or 132, wherein one or both balloons occlude a natural airway, forming a portion of the airway into which the solution is injected, and the flow of the liquid outward from the portion of the airway is suppressed, while the solution is delivered to a target site.

[0155] A 134th embodiment according to any one of embodiments 123 to 133, wherein the solution has a theoretical osmolality of 0.8 to 15 Osm / L, preferably 5 to 9 Osm / L.

[0156] A 135th embodiment according to embodiment 123, or any one of 125 to 134, wherein the one or more solutes are selected from physiologically acceptable salts and inorganic hydroxides, preferably from any of the following groups: aqueous solutions of calcium chloride, magnesium chloride, sodium carbonate, sodium chloride, sodium citrate, sodium hydroxide, or sodium nitrate, or combinations thereof.

[0157] The 136th embodiment is one of embodiments 123 to 134, wherein the solution is a hypertonic saline solution containing sodium chloride (NaCl) and water at a concentration of 3% to 30% (w / v).

[0158] The 137th aspect according to aspect 136, wherein the solution is a hypertonic saline solution containing sodium chloride (NaCl) at a concentration of 5% to 25% (w / v).

[0159] A 138th embodiment according to either embodiment 136 or 137, wherein the solution contains water and a component other than sodium chloride at a mass / volume concentration of less than 1%.

[0160] A 139th embodiment according to any one of embodiments 123 to 138, wherein the target site is formed by cancerous tissue and is 0.1 to 30 cm 3 Especially 0.5-15cm 3 It has the volume of .

[0161] A 140th embodiment according to any one of embodiments 123 to 139, wherein the solution is used during surgery using a total treatment time that is a function of the volume of the target site.

[0162] A 141st embodiment according to any one of embodiments 123 to 141, wherein the solution is used during surgery with a total treatment time of less than 7 minutes, and the solution is used for treating a target site with a diameter of less than approximately 2 cm.

[0163] A 142nd embodiment according to any one of embodiments 123 to 140, wherein the solution is used during surgery with a total treatment time of less than 10 minutes, and the solution is used for treating a target site with a diameter of approximately 2 cm.

[0164] A 143rd embodiment according to any one of embodiments 123 to 140, wherein the solution is used during surgery with a total treatment time of less than 15 minutes, and the solution is used for the treatment of a target site with a diameter of 2 cm or more.

[0165] A 144th embodiment according to any one of embodiments 123 to 140, wherein the solution is used during surgery with a total treatment time of less than 30 minutes, and the solution is used for treating a target site larger than 3 cm in diameter.

[0166] A 145th embodiment according to any one of embodiments 123 to 144, wherein the solution is in direct contact with the target site.

[0167] A 146th embodiment according to any one of embodiments 123 to 145, wherein the solution is delivered to an airway target site using any one of the systems of the preceding embodiments 1 to 87, or using any one of the catheters of the preceding embodiments 88 to 122.

[0168] A 147th aspect relates to a system for treating a targeted site in lung tissue, the system comprising: a flow regulator configured to be interposed between a conductive fluid source and a conductive fluid outlet that can be located in or near the targeted site in lung tissue, further configured to control the flow rate or bolus dose of conductive fluid flowing out of the fluid source and delivered to the conductive fluid outlet; and a controller configured to control the flow regulator and to receive a value detected by a sensor, the sensor detecting a value of a control parameter representing a physical property of at least one of the following substances present in or near the targeted site in lung tissue: temperature (T), pressure (p), electrical impedance (Z), or conductivity (C), and the controller The system is configured to receive values ​​for one or more control parameters and to control a flow regulator based on the values ​​for one or more control parameters, and controlling the flow regulator involves performing a control cycle that includes: controlling the flow regulator in a high-delivery mode where the flow rate of conductive fluid delivered to the conductive fluid outlet is greater than or equal to a set high flow rate, or the bolus dose of conductive fluid delivered to the conductive fluid outlet is greater than or equal to a set high bolus dose; and controlling the flow regulator in a low-delivery mode where the flow rate of conductive fluid delivered to the conductive fluid outlet is less than or equal to a set low flow rate, which is less than or equal to a set high bolus dose, or the bolus dose of conductive fluid delivered to the conductive fluid outlet is less than or equal to a set low bolus dose, which is less than or equal to a set high bolus dose.

[0169] Aspect 168 relates to a method for treating a target site in lung tissue, comprising: delivering ablation energy to the target site; delivering a conductive fluid to the target site during the delivery of ablation energy; detecting a value of a control parameter which is at least one of temperature (T), pressure (P), electrical impedance (Z), and conductivity (C) near the target site; and controlling the delivery of the conductive fluid by (i) controlling the flow rate or bolus dose of the conductive fluid based on the value of the detected control parameter; (ii) controlling the flow rate to be above a set high flow rate or controlling the bolus dose to be above a set high bolus dose while operating in high delivery mode; and (iii) controlling the flow rate to be below a set low flow rate or controlling the bolus dose to be below a set low bolus dose while operating in low delivery mode, wherein the set low flow rate is less than the set high flow rate, or the set low bolus dose is less than the set high bolus dose. [Brief explanation of the drawing]

[0170] [Figure 1] This is a schematic diagram of a part of the human respiratory system. [Figure 2] This is a magnified view of a portion of Figure 1. [Figure 3] This is a schematic diagram of the distal portion of an ablation device, which consists of a single occluding balloon proximal to the electrode. [Figure 4A] Figure 3 is a schematic diagram showing the position of the device within a living organism. [Figure 4B] This is a schematic diagram of an alternative embodiment having a tumor puncture wire and a puncture dilator. [Figure 4C] This is a schematic diagram of an alternative embodiment having a tapered shaft. [Figure 5A] This is a schematic diagram of the distal section of an ablation device, which consists of two occlusion balloons on the same shaft, one located proximal to the electrode and the other distal to the electrode. [Figure 5B]This is a schematic diagram of the distal portion of an ablation device, which consists of two occluding balloons, one of which is located proximal to the electrode and on the first shaft, and the other located distal to the electrode and on the second shaft extending from the first shaft. [Figure 6A] Figure 5A is a schematic diagram showing the position of the device within a living organism. [Figure 6B] Figure 5B is a schematic diagram showing the position of the device within a living organism. [Figure 7] This is a schematic diagram of the distal section of an ablation device with needle electrodes. [Figure 8] Figure 7 is a schematic diagram showing the position of the device within a living organism. [Figure 9] This is a schematic diagram of multiple catheters placed within the patient's airway to position energy transfer electrodes at various locations associated with the target tumor. [Figure 10A] Figure 9 is a schematic diagram of the cross-section. [Figure 10B] This is a plot of a multiphase waveform. [Figure 10C] This is a schematic diagram of a multiphase RF system. [Figure 10D] This is a plot of digital clocks divided to generate a multiphase RF configuration. [Figure 11] This is a schematic diagram of the system for operating an intrabronchial lung tumor ablation device. [Figure 12] These graphs show the impedance and phase during the experiment, before lung collapse, after lung collapse, and after injection of hypertonic saline. [Figure 13] This graph shows electrode temperature, power, phase, and impedance during RF transmission with hypertonic saline perfusion. [Figure 14A] This is a schematic diagram of various embodiments of occlusion devices for ablation catheters. [Figure 14B] This is a schematic diagram of various embodiments of occlusion devices for ablation catheters. [Figure 14C] This is a schematic diagram of various embodiments of occlusion devices for ablation catheters. [Figure 14D]This is a schematic diagram of various embodiments of occlusion devices for ablation catheters. [Figure 15] This is a schematic diagram of an ablation catheter having an ablation electrode between two impedance monitoring electrodes in a biological position. [Figure 16A] This is a flowchart illustrating an embodiment of the pump control algorithm. [Figure 16B] This is a flowchart illustrating an embodiment of the pump control algorithm. [Figure 16C] This is a flowchart illustrating an embodiment of the pump control algorithm. [Figure 16D] This is a flowchart illustrating an embodiment of the pump control algorithm. [Figure 16E] This is a flowchart illustrating an embodiment of the pump control algorithm. [Figure 17A] Figures 16A-16E show the resulting behavior of the pump control algorithm, plotting temperature and flow rate over time during 60W RF transmission. [Figure 17B] This is a plot of temperature, power, and flow rate over time during the transfer of power with a gradient. [Figure 18A] This is a CT image of catheter placement with a low level of air volume reduction in the target airway, as evidenced by a small white, opaque area. [Figure 18B] This is a CT image of catheter placement with a higher level of air volume reduction in the target airway, as evidenced by a larger white opaque area. [Figure 19A] This is a macroscopic pathological image of a cross-section through the left lower lobe, showing a very small area of ​​necrotic tissue one month after injection of hypertonic saline. RF energy was not applied. [Figure 19B] This is a macroscopic pathological image of a cross-section through the right lower lobe, showing the extent of larger necrotic tissue one month post-treatment, consisting of a combination of hypertonic saline injection and 90 seconds of RF transmission. [Figure 20]This is a plot of temperature, RF power, perfusion flow rate, and total cumulative volume of perfusion fluid against time for the control algorithm. [Modes for carrying out the invention]

[0171] [Detailed explanation] This disclosure generally pertains to devices and methods for ablating malignant lung tumors, and more specifically to ablating lung tumors via an approach through the patient's airway. An approach through the patient's airway may also be referred to as a transbronchial or intrabronchial approach and includes delivery medical devices that pass through the passage through which air travels from the nose or mouth to the alveoli. The term airway refers to any anatomical lumen of the respiratory system through which air passes, including the trachea, bronchi, and bronchioles.

[0172] Figure 1 is a schematic diagram of a portion of the patient's respiratory system, including the trachea 50, tracheal keel 51, left main bronchus 52, right main bronchus 53, bronchioles 54, vesicles (not shown, located in the tulipia at the end of the bronchioles), left lung 55, and right lung 56. The right main bronchus is further divided into three second bronchi 62 (also known as lobar bronchi), which carry oxygen to the three lobes of the right lung: the upper lobe 57, middle lobe 58, and lower lobe 59. The left main bronchus is divided into two second bronchi 66 or lobar bronchi to carry air to the two lobes of the left lung: the upper lobe 60 and lower lobe 61. The second bronchi are further divided into third bronchi 69 (also known as segmental bronchi), each of which gives rise to a bronchopulmonary segment. The bronchopulmonary segment is the part of the lung separated from the rest of the lung by a septum of connective tissue (not shown). As shown in Figure 2, the third bronchus 69 divides into numerous bronchioles 70, each bronchiole 70 divides into terminal bronchioles 71, each terminal bronchus 71 then gives rise to several respiratory bronchioles 72, each respiratory bronchiole 72 then divides into 2 to 11 alveolar ducts 73. Each alveolar duct has associated 5 or 6 alveoli 75. The alveoli are composed of several alveoli 74. Alveoli 74 are the basic anatomical units of gas exchange in the lung. Figure 2 also shows peripherally located tumors 80 situated outside the bronchioles and in the spaces between them. Target tumors 80 can be located peripherally, centrally, or internally in the lung or mediastinal lymph nodes or airway walls.

[0173] There are primarily two types of lung cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC accounts for approximately 85% of all lung cancers and is the most common type of lung cancer among both men and women in the United States. It includes adenocarcinoma, which forms from glandular structures within epithelial tissue and usually occurs in the peripheral regions of the lung; squamous cell carcinoma, which accounts for 25% of all lung cancers and is more commonly located in the central region; and large cell carcinoma, which accounts for approximately 10% of NSCLC tumors. The focus of this disclosure is the treatment of NSCLC, which may occur peripherally between bronchioles, centrally between bronchi, or within lymph nodes. However, the devices, systems, and methods disclosed herein may also be used for the ablation or treatment of other lung diseases.

[0174] Aspects of this disclosure provide a method for treating a lung tumor in a patient. A pathway to a point of interest in the patient's lung is generated. In the majority of patients with isolated nodules, the airway is expected to be identified by target-to-target CT, suitable for positioning an ablation energy delivery element in close proximity to the target, for example, within 1 cm. Using a pre-acquired CT as a map, a flexible instrument can be guided through the airway by a bronchoscopist using well-known existing tools. In one embodiment, an expandable working channel advances through the airway into the lung along the pathway to the point of interest. At the point of interest, the expandable working channel is positioned in a substantially fixed direction. A fixation mechanism may be used to ensure the stability of the channel. A catheter may advance through the expandable working channel to the target site in the lung. The working channel may be, for example, a lumen through a delivery sheath or through a bronchoscope, both of which may be maneuverable or incorporate a guidewire lumen. If necessary, the delivery sheath may be an intrabronchial ultrasound delivery sheath that generates an ultrasound image of the tissue surrounding the distal end of the sheath. The portion of the lung containing the target site may be occluded, for example, by occluding the airway supplying that portion (using at least one occluding element, such as a catheter or balloon on a delivery sheath), by applying negative pressure to that portion of the lung, or by applying other means to collapse the portion of the lung disclosed herein, thereby reducing at least the corresponding air volume. To ensure a reduction in air volume in the portion of the lung, electrodes on the catheter may be used to measure tissue impedance or phase. Complete collapse of the target lung site is not required. Experimental observations have shown that a reduction in air volume resulting in a 5-20% reduction in the respective bipolar impedances of the target lung site is sufficient for the purpose of facilitating effective ablation energy transfer.Lung tissue is treated using an ablation catheter at a target site in the lung by injecting hypertonic saline or other types of bioconductive salts or solutions (e.g., calcium chloride, magnesium chloride, sodium carbonate, sodium chloride, sodium citrate, sodium hydroxide, or sodium nitrate) into the target site in the lung through a catheter, and applying RF energy from one or more electrodes on the catheter. If necessary, more than one ablation catheter may be delivered to the target site in the lung, and an RF circuit may be formed between an electrode on a first catheter and an electrode on a second catheter. In embodiments of this disclosure, the RF electrode is used to deliver ablation energy.

[0175] The dilating working channel may be positioned within the patient through a bronchoscope or a portion of a bronchoscope, as needed. A localizable guide may be positioned within the dilating working channel to locate the point of interest. The biopsy tool may advance to the point of interest. Prior to the biopsy tool advancing through the dilating working channel, the localizable guide may be removed from the dilating working channel. Alternatively, a navigation guide dilating working channel may be provided by Veran Medical or superDimension TMIt may be used in conjunction with a 3D navigation system, such as one provided by Medtronic, or with a robotically controlled working channel of a bronchoscope, such as one provided by Intuitive Surgical or Auris Health. For example, the navigation device (e.g., the catheter of this disclosure) may be fitted with a shape sensor, such as a fiber-Bragg grating (FBG) sensor. The use of such a shape sensor inside the ablation catheter is described by reference to the sensor by Ho et al., “FBG Sensor for Monitoring Contact Level and Predicting Perforation in Cardiac Ablation,” 1002-1013, December 2012. Lung tissue may be biopsied. If the biopsy is confirmed to be positive, the lung tissue may then be ablated. The biopsy tool is withdrawn and replaced with an ablation catheter or tool having at least one energy transfer element. This method may facilitate the placement of the energy transfer element of the ablation catheter or tool at the same location where the biopsy is performed. Prior to treating the lung tissue, the placement of the ablation catheter at the point of interest may be confirmed, for example, by visually identifying the point of interest relative to the airway elements using a bronchoscope. Lung tissue or tumor may be infiltrating the point of interest. Effective treatment of the lung tissue may be confirmed, for example, by obtaining a post-ablation biopsy or by evaluating the impedance or phase of the tissue being treated using electrodes or sensors on the ablation catheter.

[0176] With the current resolution of CT scanners, at least seven or eight, perhaps more, generations of airways can be imaged and evaluated. There is reason to be confident that imaging resolution will improve even more rapidly. If the trachea is the starting point and a pulmonary parenchymal nodule is the target endpoint, then appropriate software can query a 3D image dataset and provide one or more pathways to the target through adjacent airways. The bronchoscopist can follow this pathway during the actual or navigational bronchoscopy procedure, and a cannula can be rapidly inserted into the precise airway pathway to the nodule using a wire, bronchoscope, and thin-walled polymer tube or channel or detected / navigated bronchoscopy instrument.

[0177] Once the access channel is positioned correctly, multiple probes can then be positioned to biopsy or ablate the identified tumor. Ultrathin bronchoscopes can be used in a similar manner. When these types of approaches are used in conjunction with navigation bronchoscopy tools, the vast majority of peripheral lung lesions can be destroyed.

[0178] Currently available fiber optic bronchoscopes (FOBs) are equipped with an illumination fiber optic bundle and an imaging fiber optic or camera. Except for a very small number of "ultrathin" bronchoscopes, channels are also present for aspirating secretions and blood, for passing topical medications and lavage fluids, and for the passage of various instruments for the diagnosis or treatment of retrieved tissue. Typical diagnostic bronchoscopes have an outer diameter of 5.0–5.5 mm and a working channel of 2.0–2.2 mm. This inner diameter channel can accommodate most cytology brushes, bronchial biopsy forceps, and transbronchial aspiration needles with sheath outer diameters between 1.8–2.0 mm. Smaller bronchoscopes with outer diameters in the 3.0–4.0 mm range, and their correspondingly smaller channels, are usually designated "P" (for pediatric use), but they can also be used in adult airways. Newer generations of thin video and fiber optic bronchoscopes have a 2.0 mm working channel with an outer diameter of 4.0 mm. One drawback of these bronchoscopes is the sacrifice of a smaller image area due to the reduced optical beam. Ultrathin bronchoscopes generally have an outer diameter of less than 3 mm. For example, the Olympus models BF-XP40 and BF-XP160F (Olympus America, Center Valley, PA) have an outer diameter of 2.8 mm and a working channel of 1.2 mm. Special instruments with appropriate inner diameters (e.g., reusable cytology brushes and forceps) are available for tissue sampling. All current-generation video bronchoscopes are constructed with a working length of 60 cm. These bronchoscopes are suitable for accessing the distal airway to position a guidewire in which the delivery channel or energy delivery catheter may be replaced.

[0179] Navigation bronchoscopy (NB) consists of two initial stages: planning and navigation. In the planning stage, a pre-acquired CT scan is used to mark and plan the route to targets within the lung. In the navigation stage, these pre-planned targets and routes are displayed and can be used for navigation and access to deep within the lung. Once the target is reached, NB enables multiple uses within the same procedure. The patient's chest CT scan is loaded into specialized software that reconstructs the patient's airway in multiple 3D images. The physician uses these images to mark target locations and plan the route to these target locations within the lung. Using the planned route and real-time guidance generated in the planning stage, the physician navigates the detection probe and dilating working channel to the desired target location. Once the desired location is reached, the physician locks the dilating working channel in place and the detection probe is removed. The dilating working channel provides access to the target node for bronchoscopy instruments or catheters.

[0180] [Decreased air volume in a portion of the target lung tissue]

[0181] As shown in Figure 1, the lung is divided into five lobes, including the right upper lobe 57, the right middle lobe 58, the right lower lobe 59, the left upper lobe 60, and the left lower lobe 61. The lobes are then divided into segments. Each lobe or segment is generally autonomous and receives its own bronchial and pulmonary artery branching. If the airway that gives rise to a lobe or segment is blocked by a one-way valve or an occluding device and air is drawn out, it will undergo collapse or a reduction in volume, leading to local tissue compression under the pressure exerted by the rest of the lung. Unlike most tissues in the body that are susceptible to tumors, lung tissue is inherently very flexible, compressible, and can ultimately be collapsed. Atelectasis refers to the complete or partial collapse of the lung, a lobe, or a segment of the lung. When the airway is blocked, the negative pressure exerted on the target area of ​​the lung is absent or reduced. Therefore, adjacent areas or segments compress it and remove the trapped air. Alternatively, or additionally, vacuum suction may be applied through a lumen in a blocking device (e.g., a balloon). Vacuum may be used to further remove air from the target lung area. As a result, further or more effective collapse may be achieved. For the purposes of this disclosure, “collapse a portion of the lung” means compressing or reducing the corresponding amount of air, or contracting a portion of the lung, and does not necessarily mean complete collapse. The lung will contract even without more air. In some cases, collateral ventilation may reinflate the collapsed area, but it is understood that the tissue contracting due to increasing heat and continuous suction is likely to overcome, at least partially, the reinflation of the target area. The balloon may be used to block entry into the target airway when inflated. The lumen through the balloon may be used to provide further vacuum suction.

[0182] Lung compliance is a key characteristic of the lungs. Various lesions affect compliance. In particular, relevant to cancer ablation, it is believed that fibrosis is associated with decreased lung compliance, emphysema / COPD may be associated with increased lung compliance due to a decrease in alveolar and elastic tissue, and that lung surfactant increases compliance by lowering the surface tension of water. The inner surface of the alveoli is covered with a thin film of fluid. The water in this fluid has high surface tension, giving it a force that can collapse the alveoli. The presence of surfactant in this fluid disrupts the surface tension of the water, which reduces the likelihood that the alveoli will collapse inward. If the alveoli collapse, considerable force will be required to expand them, meaning that compliance will be significantly reduced. Atelectasis, clinically defined as collapse of a region of the lung visible on X-ray, is generally undesirable. However, localized lung collapse may be advantageous in the treatment of emphysema and in targeted lung cancer ablation, as suggested by the authors. The advantages of collapsing or reducing the air volume of a target lung site, including the target tumor, during tumor ablation may include: bringing electrodes placed within the airway surrounding the tumor closer to the tumor, thereby improving the concentration of ablation energy or enhancing the effectiveness of tumor ablation; making the transfer of ablation energy and heat propagation more efficient by removing air from collapsed or contracted lung tissue supplied by the airway; causing hypoxia that leads to localized hypoxic lung defect contraction and localized anemia in the lung segment, reducing metabolic cooling and improving the efficient use of thermal energy; and allowing the spread of perfusion fluids such as hypertonic saline to limit the target area, thereby ensuring that most of the effects of virtual electrode ablation are delivered to the target site. However, complete collapse of the lung, lobe, or lung segment is not intended by the present invention. Reducing the bronchial air volume via vacuum application to the catheter generally improves electrical contact between the RF electrode and the bronchial wall.This, in turn, improves safety and reduces the ineffectiveness of energy transfer that can occur due to evaporation of the perfusion fluid (caused by overheating) or its inadvertent spread to adjacent tissues, allowing electrode contact with tissue to become more constant and potentially have a larger contact area. Furthermore, ablation energy, such as high-frequency electrical energy, can be delivered by a computer-controlled ablation console, and the collapse of lung tissue can improve temperature-controlled ablation performance by improving contact stability and increasing the pressure between the tissue and the electrode. For example, in a collapsed or constricted airway, a temperature sensor placed in or on the electrode can provide more accurate temperature feedback to a computer-controlled ablation console used to control energy transfer parameters such as RF power, RF power increase gradient, or duration, while improved contact stability and increased pressure can allow the temperature sensor to improve the stability of thermal and electrical conduction, enabling a more accurate representation of the temperature of the tissue surrounding the electrode. As a result, the ablation energy delivered to the target lung tissue and tumor can be optimized, and the temperature of the target tissue can be heated to the intended temperature setpoint in an efficient and safe manner.

[0183] A reduction in the volume of air in a lobe, segment, or other section of the lung, as determined by the morphology of the airways and the air supply through the airways, can be hindered by interlobular collateral ventilation, which is common in patients with incomplete interlobular fissures, partially damaged, and destroyed lungs. As an alternative method to segmental or lobe collapse, heating of lung tissue or injection of chemicals, foamy substances, or high-temperature steam into a target segment or lobe may be employed. For example, injection of high-temperature steam into an enclosed space such as a lobe or segment results in the collapse of the space. The properties of the lung are that when a segment collapses, a pressurized adjacent segment compresses it and fills the volume vacated by the collapsed space. Techniques for collapsing or partially collapsing a part of the lung with collateral air pathways using a bronchoscope and bronchoscopic delivery devices are described, for example, in U.S. Patent US7412977B2. Partial collapse of the lung, particularly the upper lobe, has been previously proposed to mimic the results of lung decompression surgery in advanced emphysema, but not to enhance thermal ablation (e.g., RF) of tumors. Proposed techniques included closure plugs and valves, and the injection of steam (e.g., heat), foam, and glue into the airway. Mechanical compression of the lung area using springs or wire coils has also been proposed. All of these methods can be envisioned as being modified and employed for cancer treatment in any lobe or segment in which a tumor is identified on CT and identified as malignant. As mentioned above, partial collapse of the lung or lung area is not required to successfully carry out the invention. The objective is to reduce the volume of bronchial air to improve contact between the electrode and tissue.

[0184] Ultimately, the entire lung can be temporarily collapsed using an independent lung ventilation technique. The lung is intubated and ventilated via a separate endotracheal tube with occlusions for both main tracheae. A patient healthy enough to tolerate this can breathe using mechanical ventilation of only one lung while the contralateral lung is collapsed and operated on. Electrodes may be placed prior to de-airing and collapsing the lung. In such cases, collateral ventilation would not significantly affect the operator's ability to collapse the lung.

[0185] Reducing the volume of air in a portion of the target lung can bring other benefits, such as facilitating tumor ablation by increasing the size of the RF ablation lesion. Air in the lung airways is a very poor heat conductor and conductor. Collapse of the airway (e.g., by obstructing the airflow or by other methods described herein) is to remove the air, which improves the permeability of RF through already ablated tissue. The inventors therefore propose reducing the volume of air in a target lung site as a means of easily improving energy transfer through electrodes combined with devices such as bronchial catheters. Balloons (e.g., filled with liquid or gas), another space closure plug, a deployable valve, injected steam, a fan, glue injection, or a stent may be used to occlude the airway to reduce the volume of air in a specific lung site surrounding or adjacent to a target tumor. A balloon can be used, for example, to occlude a portion of the airway, and when the airway is blocked, the blood absorbs the gas inside the alveoli, thus reducing the volume of air. Alternatively, trapped air may be aspirated using vacuum pressure through a lumen in the catheter. Suction may be applied for 30 seconds to 10 minutes, depending on the desired level of contraction or collapse. When the airway is deprived of air, the alveoli contract. In some cases, blood, fluids, and mucus may fill, at least partially, the already ventilated space, allowing the space to conduct RF energy and heat more efficiently.

[0186] In addition, segmental collapse leads to hypoxia, which results in localized hypoxic vasoconstriction of the lungs. Reduced blood flow to the target area of ​​the lungs leads to slower blood velocity and metabolic cooling, resulting in more efficient use of thermal energy.

[0187] A procedure for ablation of a lung tumor, which involves collapsing a target site in the lung using a catheter configured to occlude the airway and ablate tissue, includes the following steps: locating the target tumor in the lung (e.g., using medical imaging techniques such as CT); generating a 3D navigation map by registering the medical images with navigation technology; delivering a bronchoscope through the patient's airway and positioning its distal end near the target lung site, using 3D navigation or electromagnetic navigation assistance as needed; taking a biopsy to confirm the tumor's location; applying lubricant to the bronchoscope, occlusion / ablation catheter, and endotracheal tube lumen; positioning the occlusion / ablation catheter through the bronchoscopic working channel; delivering the catheter via a guidewire as needed; guiding the distal end of the catheter to the target site; navigating the ablation electrode as close to the tumor as possible (e.g., by standard, virtual, or navigation bronchoscopy); and measuring the electrode's position or contact as needed. Confirmation using impedance, imaging or EM navigation, and, if necessary, positioning an occlusion balloon in the airway proximal to the ablation site, inflating the occlusion balloon while visualizing it with a bronchoscope lens, and, if necessary, allowing a reduction in the amount of air in the target site of the lung by absorbing air or applying other bronchial air volume reduction steps as disclosed herein (e.g., applying suction to remove air from the target lung site), and, if necessary, monitoring the electrical impedance of the tissue (e.g., between the RF electrode and the grounding pad, or between the bipolar RF electrode), where a stable and constant impedance indicates a reduction in bronchial air volume, and therefore increasing the contact of the tissue with the electrode (e.g., in studies conducted by the inventors, impedance decreases by approximately 24% to 38% when bronchial air volume decreases), perfusing the electrode or injecting a conductive fluid into the target lung site, and transmitting computer-controlled ablation energy to the target tissue through the electrode, and, if necessary, removing any fluid remaining in the lung site.This may include removal via catheter or bronchoscope, deflation of the occluding balloon, removal of the catheter from the patient, and visualization of the treated airway for signs of bleeding or blistering, which may be treated if necessary. If necessary, subsequent ablations may be performed at a different location by moving the ablation electrodes to a different position. If the lung is pre-collapsed and it is difficult to reposition the electrodes while the lung area is collapsed, it will be necessary to inflate the lung area before moving the ablation electrodes. In some situations, it may be possible to keep the lung area deflated and filled with conductive fluid as needed while repositioning the electrodes. If necessary, alignment markers may be placed on or around the tumor to determine if the tumor was successfully ablated or to later locate the tumor using CT for application of subsequent ablations.

[0188] Figures 18A and 18B are CT images of the lungs during animal experiments, illustrating examples of varying degrees of bronchial air volume reduction. In Figure 18A, vacuum aspiration was not efficient in relatively reducing bronchial air volume. As a result, the white opaque region 800 (indicating the volume of lung tissue affected by bronchial air removal) was limited in size and concentrated only in the space surrounding the RF electrode 234. This observation correlates very well with a relative decrease in catheter bipolar impedance (measured between the proximal electrode 237 and the RF electrode 234, see Figure 4A). In baseline, the bipolar impedance was 590 Ω before the application of catheter vacuum aspiration. After the application of vacuum aspiration, the bipolar impedance remained unchanged at 590 Ω. Conversely, Figure 18B shows a state where catheter vacuum aspiration was more successful in reducing bronchial air volume. As a result, the white opaque region 800 expanded and included a larger area around the catheter RF electrode 234. These observations also correlate well with the changes measured by the catheter bipolar impedance. At baseline, the bipolar impedance was 670 Ω before aspiration. After vacuum application, the bipolar impedance decreased to 400 Ω, representing a 40% decrease from the baseline. A 5-50% decrease in bipolar impedance from the baseline is usually sufficient to indicate improved electrical contact between the bronchial wall and the RF electrode 234. For further improvement of the quality of electrical contact between the RF electrode and the target bronchial wall, a small amount of hypertonic saline was released before RF transmission. For example, in the cases shown in Figures 18A and 18B, the release of 23.4% hypertonic saline at a rate of 5 ml / min for a duration of 5 seconds reduced the catheter bipolar impedance to 140 Ω and 130 Ω, respectively. Preferably, without limiting the scope of the present invention, the bipolar impedance should be reduced to less than 300 Ω before RF energy transmission. As shown in Table 1, a greater reduction in bronchial air volume (Figure 18B) resulted in improved RF electrode contact and a larger ablation volume (width 1, width 2, and length listed in Table 1). The increased ablation volume was not solely a result of the greater reduction in bronchial air volume.The increased flow rate of hypertonic saline created a larger virtual RF electrode, likely as a result of localized blood and air flow conditions. This larger virtual RF electrode, as expected, contributed to the formation of a larger ablation area. [Table 1]

[0189] [Delivery of conductive fluid to the target lung site]

[0190] The conductive fluid may be delivered to the airway of the target site in the lung (e.g., via the lumen of the ablation catheter) to enhance RF ablation. The delivery of the conductive fluid may be a large injection of hypertonic saline (e.g., hypertonic saline with a concentration in the range of 5% to 30%) to enhance intrabronchial lung tumor ablation by ablating larger volumes of tissue (e.g., ablation of 1.5 cm or more in diameter). Other conductive fluids may be used. For example, several biocompatible conductive aqueous solutions (e.g., conductive solutions that are not inherently lethal or toxic to the body) such as calcium chloride, magnesium chloride, or sodium hydroxide may be used. Such solutions have an electrical resistivity (70 to 225 mS / cm, if expressed as conductivity) in the range of 2 to 35 Ω·cm, preferably 4 to 14 Ω·cm, at a volume concentration of 10% or more, which is low enough to support the efficient conduction of high-frequency current. The osmolality is an important property of such an aqueous solution, which can be calculated as follows:

number

[0191] Solutions with higher osmolality may be preferred. In the calculation of the theoretical osmolality of saline, the osmotic coefficient φ = 1.

[0192] If necessary, the conductive fluid may have a high viscosity, or may be injected in a low viscosity state into the target site and change to a high viscosity state at the target site in the body. For example, ionic salts such as NaCl or others as described above may be mixed with a reverse phase transition polymer and water, which may change to a higher viscosity when transitioning from a temperature below body temperature to body temperature. Polymers with appropriate properties may be, for example, block copolymers such as PLGA - PEG - PLGA composed of polyethylene glycol, which is esterified by covalent bonds at both ends with an FDA - approved lactic acid - glycolic acid copolymer. Other examples of polymers may be based on polyethylene glycol, albumin, silk, wool, chitosan, alginic acid, pectin, DNA, cellulose, poly(sialic acid), dendritic polylysine, lactic acid - glycolic acid copolymer (PLGA), gellan, polysaccharides, and poly(aspartic acid), and combinations thereof. The mixture may be designed to add high viscosity characteristics by the polymer while maintaining a high conductivity based on hypertonic saline. In this way, good control can be effectively achieved through the spread of the conductive fluid. The polymer may be biodegradable, biocompatible or bioabsorbable. The ionic component may be, for example, M + X - or M 2+ Y 2-It may also include, where M belongs to an alkali or alkaline earth metal such as Li, Na, K, Rb, Cs, and X is a halogen, acetate, and M + This indicates other equivalent counters that balance it, where Y is X2 or a mixture of halogens, acetates, carbonates, sulfates, phosphates, and M 2+It may also be other equivalent counters that balance it, and may be formic acid, glycolic acid, lactic acid, propionic acid, caproic acid, oxalic acid, malic acid, citric acid, benzoic acid, uric acid, and their corresponding conjugate bases. The conductive fluid may further contain components such as pharmaceuticals (e.g., anti-cancer or antibiotic) to aid in tissue healing or further treatment of cancer cells, or X-ray contrast agents. The amount injected should be sufficient to penetrate beyond the target airway and into the alveoli and lung parenchyma. This is achieved by conducting the delivered ablation energy (e.g., RF or microwave) to more tissue than the surface of the electrode contact, thereby substantially increasing the effective electrode size (i.e., creating a virtual electrode) and creating a more stable and permanent electrical contact with the tissue. Conductive fluids such as hypertonic saline or others may also be able to deliver ablation energy more efficiently, as less power is lost in saline and more is delivered to the tissue. Hypertonic saline has significantly increased conductivity and therefore lower contact impedance, so less power is lost to hypertonic saline compared to physiological saline. Because less power is lost to hypertonic saline, it is less likely to reach its boiling point. Therefore, in lung areas with reduced bronchial air volume, ablation produced with hypertonic saline tends to produce greater damage, although it does not exhibit char formation. Injection of the conductive fluid may be carried out using the methods and apparatus described herein for fluid injection and any concurrently occurring withdrawal, along with, if necessary, collapse of the target lung area around the electrodes. An example of apparatus 220 configured to collapse the lung area and occlude the target area of ​​the lung for ablation using perfusion electrodes is shown in Figure 4A, which comprises at least one electrode 234 having at least one perfusion port 235. As shown in Table 1, a higher flow rate of hypertonic saline during a 6-minute RF transfer, as depicted in Figure 18B, resulted in a larger ablation volume. As shown in Figure 17 and the related text, the flow of hypertonic saline during RF transmission is controlled by an embodiment of the algorithm of this disclosure.While the algorithm is intended to optimize the total amount of hypertonic saline, a minimum amount is required to generate an ablation volume of an appropriate size for treating lung cancer. For example, without limiting the scope of this disclosure, a low flow rate of 0.5 ml / min from the case depicted in Figure 18A resulted in a smaller ablation volume. It is preferable to achieve a flow rate greater than 0.2–0.5 ml / min during RF transmission. A flow rate of hypertonic saline exceeding its maximum value (e.g., approximately 15 ml / min) will not result in a larger ablation volume, as the saline will reach a point where it inefficiently wastes RF energy. Therefore, the algorithm in Figure 17A will optimize the flow rate of hypertonic saline to maintain its total amount below the maximum value but greater than the minimum value mentioned above. A flow rate of hypertonic saline in the range of 0.2–5 ml / min, preferably in the range of 1.5–2.5 ml / min, is expected to be effective in generating a sufficiently large ablation volume. The average flow rate of the conductive fluid maintained during the treatment session may be in the range of 0.1–15 ml / min.

[0193] Animal studies have shown that a combination of injecting hypertonic saline into the airways and transferring thermal energy to the airways via radiofrequency has a significant tissue-killing effect, as seen in CT scans taken two weeks post-surgery. Several previous studies have shown that hypertonic saline can significantly weaken the adhesion of tumor cells to endothelium by inhibiting the development of adhesion molecules and laminin. (Shields CJ1, Winter DC, Wang JH, Andrews E, Lang WE, Redmond HP, Department of Surgery, College Cork Hospital and National University of Ireland, Wilton. Hypertonic saline interferes with tumor cell-endothelial cell interaction by reducing the development of adhesion molecules and laminin. Surgery. 2004 July 136(1):76~83.) This may halt the metastatic behavior of tumor cells that fall off during surgery. Other studies have reported similar research using saline to induce cell apoptosis. Researchers have conducted studies using salt to kill cancer cells. They have created a technique that can induce self-destruction by injecting salt into cancer cells. (Busschaert, N., Park, S., Baek, K., Choi, Y., Park, J., Howe, E., Hiscock, J., Karagiannidis, L., Marques, I., Felix, V., et al. (2017). Synthetic ion transporters that disrupt autophagy and induce apoptosis by disrupting the chloride concentration in cells. Nature Chemistry, 9(7), 667-675.) (Ko, S., Kim, S., Share, A., Lynch, V., Park, J., Namkung, W., Van Rossom, W., Busschaert, N., Gale, P., et al. (2014). Synthetic ion transporters can induce apoptosis by promoting the transport of chloride anions into cells. Nature Chemistry, 6(10), 885-892. Unfortunately, when cells become cancerous, they change the way they transport ions across the cell membrane, in a way that blocks apoptosis.However, it should be expected that increasing the temperature can improve the diffusivity of hypertonic saline (HTS), and therefore its ability to transport HTS into cells, and that the injection of heated HTS or other salines may be a very promising direction that could have a beneficial effect in killing tumor cells. As mentioned above, other biocompatible, conductive, aqueous solutions may be employed. Higher osmolar concentrations would support better ion diffusion across the cell membrane.

[0194] High-temperature hypertonic saline (HTS) or all other high-temperature solutions from those mentioned above have good performance in osmosis or diffusion for transporting HTS to cells and can enhance the promotion of cellular dehydration. Increased extracellular salt leads to water loss from adjacent cells. As a result, high-temperature HTS enhances the cell drying effect produced by the transfer of RF energy. In contrast, studies conducted using a standard existing ablation catheter (Thermocool) powered at 50W, perfusing with room temperature saline at a high perfusion rate (30 ml / min), resulted in less cell death. HTS at concentrations above 5%, e.g., 10%, can be injected into the target space, and then an RF current is transferred through it into the tissue, so that a specific temperature, e.g., in the range of 60°C to 115°C, is reached by an electrode located distal to the catheter. Alternatively, isolated areas of the lung can be directly perfused with heated HTS through a perfusion port on the catheter. An isolated area of ​​the lung may be exposed to heat and HTS for a duration of at least 2 minutes, or appropriately 30 seconds to 30 minutes, after which the HTS and local area may be cooled by stopping the electrodes and perfusing or replacing with room temperature saline, or by draining directly through the perfusion port. This procedure may be repeated until the desired ablation result is achieved. It should be expected that increasing the temperature can improve the diffusivity of HTS and therefore the ability to deliver HTS to cells, and that injecting heated HTS or other saline may be a very likely direction that may have a beneficial effect in killing tumor cells.

[0195] Figures 19A and 19B are images of dissected lung tissue from animal experiments, illustrating an example of necrotic progression in lung tissue as a result of hypertonic saline injection and RF energy application. Figure 19A shows a case in which 23.4% hypertonic saline was injected at a rate of 3 ml / min for 10 minutes. RF energy was not applied. Hypertonic saline was delivered to the left lower lung of the animal. The animal survived for one month. Histopathology was then performed. The macroscopic pathological image shown in Figure 19A shows necrotic point 805, approximately 0.5 mm in size. Necrotic point 805 tended to enlarge slightly in the acute phase after injection, but was gradually reabsorbed into the animal's body over the following month. No safety issues of note were present in this animal. Blood electrolytes, such as Na levels, did not change relative to preoperative reference values. Blood pressure and other vital signs were all normal. No bacterial colonies were observed in high-magnification histopathology. The presence of even smaller necrotic points is an indication of the potential therapeutic effect of hypertonic saline. When combined with the delivery of RF energy, the therapeutic effect of hypertonic saline is enhanced. For example, as shown in Figure 19B, the combined effect of RF energy and hypertonic saline resulted in a necrotic area of ​​approximately 5 mm, about 10 times larger than that in Figure 19A. In the case of Figure 19B, as in the case of Figure 19A, the same amount of 23.4% hypertonic saline was delivered to the right lower lung. The same flow rate of 3 ml / min was used for 10 minutes. In addition, 10 W of RF power was applied for 90 seconds during the saline delivery period. The same animal was treated in the same way as in the case of Figure 19A. Therefore, the combined effect of RF energy and hypertonic saline injection can result in an increased necrotic area when ablating tissue in the lung, such as tumors, and thus lead to improved therapeutic outcomes.

[0196] The composition of the conductive fluid, such as HTS, may be adjustable so that the electrical or thermal conductivity or viscosity of the HTS can be adjusted. For example, the conductive fluid source may comprise multiple sources that can be combined to adjust the properties of the conductive fluid injected into the target site in the lung. A software-driven controller may be programmed to mix the multiple sources in predetermined or automatically determined proportions before or during the injection of the mixture into the natural airway of the lung at the ablated target site. For example, separate pumps may be driven at controlled proportions and durations to selectively acquire desired amounts of each of the multiple sources. The multiple fluids may be delivered to a mixing chamber prior to the delivery of the mixed fluid through the device to the target site, or they may be delivered directly to the target site simultaneously or sequentially. The automatic determination of the ratios of the multiple sources may be calculated by the controller using input from sensors located in the distal region of the device, for example.

[0197] Alternatively, multiple fluid sources with varying properties, such as salines with varying salinity concentrations, may be provided, and the controller may select which source to pump from in order to perfuse without mixing the solutions. The controller may select the fluid source based on the time in the ablation procedure, the total cumulative amount of fluid delivered to the patient, or feedback from sensors such as impedance or temperature. In one example, the first source may contain hypertonic saline (e.g., saline with a salinity concentration greater than 10%, greater than 15%, greater than 20%, or about 23.4%), and the second source may contain saline with a lower salinity concentration (e.g., 0.9%). During the initial stages of the ablation procedure, fluid may be pumped from the first source to perfuse into the target lung space, and during the second stage of the ablation procedure, fluid may be pumped from the second source to perfuse. The rationale is that hypertonic saline may be pumped to initiate the ablation and to prepare the environment in the target lung space in terms of conductivity, but its high salinity may cause edema in the lungs. Excessive edema is undesirable. After the first phase of perfusion ablation (e.g., less than 2 minutes, less than 2.5 minutes, less than 25% of the total ablation duration), the tissue environment should be adequately prepared so that a low saline solution can perform the temperature regulation work without the disadvantage of causing excessive edema. If necessary, the controller may detect, for example, by measuring impedance, whether conductivity drops to a predetermined level with a lower saline solution, and may switch back to a higher saline solution.

[0198] If necessary, the controller may adjust the ablation energy transfer parameters (e.g., flow rate of the conductive fluid, ablation energy power, set temperature, ramp rate, duration) based on various properties of the conductive fluid, such as conductivity, viscosity, temperature, or pressure. For example, adjusting at least one of the flow rate or conductivity of the conductive fluid may include adjusting at least one of the flow rate or conductivity to maintain a value detected by a temperature sensor within a defined temperature range, where the defined temperature range is optionally 60–115°C or above a certain temperature threshold, where a preferred temperature threshold is optionally 75–105°C, e.g., 85–99°C. In another example, the system is configured to adjust the conductivity of the conductive fluid in the range of 10 mS / cm to 450 mS / cm at a reference fluid temperature of 25°C.

[0199] For example, as shown in Table 1, a 6-minute transmission with an average RF power of 67W corresponds to an average tissue temperature of 90°C and a distance of approximately 27cm (4.4cm × 3.1cm × 3.9cm). 3 This results in an ablation volume. Furthermore, any aqueous solution of hypertonic saline or any other solution from those mentioned above (e.g., calcium chloride, magnesium chloride, sodium hydroxide, etc.) is also known to be toxic to cancer cells and can chemically ablate tumor cells, either alternatively or additionally. The saline that has permeated the lung parenchyma can replace the alveolar air or spread around the alveoli through the cone holes and Lambertian tubes. The perfused hypertonic saline will be doped with a non-ionic iodine contrast agent for visualization by computed tomography (CT). Other conductive perfusion fluids that can be imagined include aluminum sulfate, etc. To continuously supplement the perfusion placed in the ablation area, generating a flow of conductive fluid using suction during ablation will further promote tumor ablation by removing the heat generated in the fluid.

[0200] Various liquids can be mixed under computer control to produce a controllable, programmable, and predictable concentration of conductive ions. Alternatively, a non-flowing conductive fluid deposited in the target lung tissue would facilitate the generation of sufficient damage to ablate the target lung tumor. The desired ablation volume, which may be a function of, for example, tumor size, the distance between the target tumor and the RF electrode, or proximity to vulnerable non-target structures, may determine whether the injection of the conductive fluid is flowing or stagnant, where stagnant injection may be used for smaller ablations and flowing injection for larger ablations, and if necessary, higher flow rates or cooling of the injected fluid may be used for even larger ablations.

[0201] A conductive fluid may be injected before the start of ablation to prepare the lung for ablation and allow the fluid to flow into the tissue. Delivering a conductive fluid, such as hypertonic saline, may allow the ablation energy console to operate at a wider range of power levels as needed to achieve the therapeutic objective.

[0202] Figure 13 shows an example of the ranges for proximal electrode temperature 303, perfusion distal electrode temperature 304, power 305, impedance 306, and phase 307 achieved by injecting hypertonic saline at a rate of 1 ml / min. The temperature may be controlled within a range greater than 60°C and less than 115°C (e.g., less than 105°C, less than 100°C), or may fluctuate outside such a range for a limited period (e.g., less than 1 second, less than 2 seconds, less than 3 seconds).

[0203] If necessary, the conductive fluid may be injected into the parenchyma or tumor through a needle catheter placed in the airway, which may allow the conductive fluid to be delivered to the target site more effectively or selectively. The needle may further include an RF electrode equipped with relevant temperature and impedance sensors, which can be used to directly transmit RF energy to the parenchyma or into the tumor near the tumor.

[0204] If necessary, the injection of a conductive fluid solution, such as hypertonic saline, may be gradually increased to adjust the ablation size. As mentioned above, a hypertonic saline flow rate of 0.2–5 ml / min is expected to contribute to the formation of a sufficiently large ablation volume while maintaining the patient's electrolytes, blood pressure, and fluid load within a normal and safe range. Gradual increases may be made by adjusting the saline concentration, the amount of hypertonic saline injected, or by adjusting the position of the occlusion structure to block lung sites of varying sizes. The higher the saline concentration, the more conductive it is and the greater the damage it can produce. The larger the volume of saline injected, the more it can spread to a larger volume of tissue and produce greater damage. Larger areas of the lung being occluded can accept larger volumes of injected hypertonic saline, which can result in greater damage. RF transfer parameters may be adjusted in accordance with the gradual increase of hypertonic saline. For example, the saline concentration of the perfusion fluid may be increased in response to undesirable fluctuations in impedance values.

[0205] [Embodiment #1 (Ablation electrode on a single shaft for placement in the airway)]

[0206] An example of a device 220 configured to be delivered through a working channel, occlude a target site in the lung, reduce the amount of air in the target site, deliver a conductive solution into the target site in the lung, monitor tissue properties, and ablate a tumor is shown in Figure 3. The device in Figure 3 is shown in its in vivo position in Figure 4A.

[0207] The device 220 comprises an elongated shaft 229 having a proximal portion intended to remain outside the patient's body and a distal portion 215 intended to be delivered through a working channel to a target site in the lung proximal to the target lung tumor. The distal portion 215 is configured to be delivered through a working channel (e.g., the working channel 225 of a bronchoscope 221, or the lumen of a sheath 213 that can be delivered through the working channel of a bronchoscope). For example, a typical bronchoscopy working channel may have an inner diameter of 2.8 mm and a length of 60 cm. A delivery sheath 213 suitable for delivery through a 2.8 mm bronchoscopy working channel may have an outer diameter of less than 2.8 mm, preferably about 1.95 mm ± 0.05 mm, an inner diameter of about 0.45 mm smaller than the outer diameter, preferably about 1.5 mm ± 0.05 mm, and a length longer than the length of the bronchoscope (e.g., longer than 60 cm, preferably about 105 cm). Other dimensions may be applicable for similar catheters suitable for passing through bronchoscopy working channels of various sizes. In its delivery state, the device 220 may have a maximum diameter smaller than the inner diameter of the sheath 213 through which the device is delivered, for example, 2 mm or less (e.g., 1.5 mm or less, preferably 1.4 mm ± 0.05 mm). The device 220 may have a length longer than the length of the delivery sheath, for example, 50 cm or more (e.g., 60 cm or more, 105 cm or more, preferably about 127 cm). The shaft 229 of the device 220 may be formed, for example, from an elongated tube of Pebax 720 having an outer diameter of about 1.35 mm. The shaft may be a flexible shaft that can be traversed through the curved portion such that the curved portion of the shaft has a radius of curvature of only 7 mm. The shaft may include a wire braid that provides flexibility, pushability, torsional resistance, and torqueability.

[0208] If necessary, the device 220 may also be equipped with a guidewire lumen 236 (for example, a polyimide tube with an inner diameter of 0.015 inches passing through a lumen in the shaft 229) through which the device may be delivered via a guidewire 227, or components such as a reinforcing wire, or a tumor drilling wire, or an optical fiber wire or other device may be delivered through the lumen.

[0209] Alternatively, as shown in Figure 4B, a tumor-perforation-wire 248 having a sharp distal end 249 may advance through a guidewire lumen 236 to protrude from the distal end of the catheter 220 to facilitate penetration of tissue such as a tumor 80 that obstructs or invades the airway. The device 220 shown in Figure 4B is identical to the device in Figure 4A, except that it has a tapered distal end 247 having a lumen 236 protruding from the tip of the tapered distal end 247. The tapered distal end 247 may be used as a dilator that enters the hole in the tissue created by the tumor-perforation-wire 248 and can dilate the hole so that the ablation electrode 234 can advance into or through the hole. If necessary, the tumor-perforation-wire 248 may have a depth marker on its proximal end to indicate that the sharp distal end 249 is in close proximity to the distal end of the catheter 247. If necessary, the tumor-perforation-wire 248 is made of radiopaque material or has a radiopaque marker near its sharp distal end 249. In use, the catheter 220 may advance through the patient's airway without the tumor-perforation-wire 248, which allows the catheter 220 to pass through narrow curves more flexibly and easily. If necessary, a guidewire may be used to facilitate catheter delivery. If the target tumor is at least partially within the airway and prevents the catheter from advancing further, the tumor-perforation-wire 248 may advance through the lumen 236 until its sharp distal end 247 approaches the opening, as indicated by a depth marker if necessary. The sharp distal end 247 then advances into or through the tumor, under bronchoscopic guidance or other medical imaging or robotic guidance if necessary, to monitor its advancement and avoid the risk of puncturing the pleura or other non-target tissue. If necessary, the tumor-perforation-wire 248 may be configured to advance a predetermined distance (e.g., approximately 3 cm or less, approximately 2 cm or less, approximately 1 cm or less, approximately 5 mm or less) from the distal end of the catheter 220. The catheter 220 may advance so that its tapered end 247 expands the hole in the tumor formed by the tumor-perforation-wire 248 and the ablation electrode 234 enters the tumor 80.The tumor-perforation-wire 248 may be removed before the ablation energy is delivered.

[0210] Alternatively, a shaft reinforcing wire may advance through a lumen within the shaft, such as the guidewire lumen 236, to improve the rigidity of the catheter during placement. Although the catheter shaft is very flexible and can pass through airway curves with a radius of curvature of only 7 mm, greater rigidity may be required when advancing to avoid twisting.

[0211] If necessary, the sheath 213 may have depth markers 415 arranged along its length or a portion of its length (e.g., at least the proximal 5 cm and distal 5 cm of the sheath length) at regular intervals (e.g., about 1 cm from center to center with a width of about 1 mm). If necessary, the shaft 229 in the embodiment shown in Figure 4A or the shafts 429, 529 in other embodiments shown in Figure 5A or 5B may have depth markers 416 arranged along its length or a portion of its length (e.g., at least the proximal 5 cm and distal 5 cm of the shaft length) at regular intervals (e.g., about 1 cm from center to center with a width of about 1 mm). Depth markers may be added to the sheath or shaft using methods well known in the art, such as pad printing or laser etching. During use, the physician may position the working channel (e.g., a bronchoscopic working channel) within the patient's lung, and depth markers on the sheath or shaft may be used relative to the working channel to locate the position of the ablation electrode or occlusion device relative to the working channel.

[0212] The device 220 is configured to temporarily, and at least partially, occlude an airway that delivers air to a target lung site. As seen in Figures 3 and 4A, the device 220 comprises an occlusion element such as an inflatable balloon or an occluder 231. An elongated shaft 229 comprises a lumen 222 (e.g., a polyimide tube with an inner diameter of 0.015 inches passing through the lumen in the shaft 229) having a port 232 located inside the occluder 231 for inflating and deflating the occluder. The occluder 231 may be a balloon (e.g., a compliant balloon) of a size that occludes an airway or an airway of a certain diameter range (e.g., a diameter ranging from 3 mm to 10 mm). The occluder 231 may be inflated by an injection fluid (e.g., a gas such as air, a liquid such as water or saline solution, or a control solution) that enters the occluder 231 through the lumen 222. If necessary, the fluid may be injected manually using a syringe connected to the proximal part of the device 220, and the fluid pressure may be maintained by closing a lockstop valve. The occluder may be removed and deflated by opening a lockstop valve and using a syringe to aspirate the expansion fluid from the balloon. Alternatively, the system operating the device may include a pump for injecting or removing the fluid to inflate or deflate the balloon. If necessary, a second port communicating with a second lumen may be located within the occluder to allow the expansion fluid to be injected into and removed from the occluder, thereby allowing the fluid that maintains the expansion pressure to circulate within the occluder, which helps to keep the temperature of the occluder below the ablation temperature and avoids the risk of thermal damage to the occluder.

[0213] The occluders 231 shown in Figures 3 and 4, or similar occluders 431, 481 shown in Figure 5A, 531, 581 shown in Figure 5B, and 231 shown in Figure 7, may be compliant, semi-compliant, or non-compliant inflatable balloons. Compliant balloons are preferably made of a material that can avoid damage at temperatures up to at least 120°C for at least 30 minutes and can withstand inflation of 1 cc of air for at least 30 minutes. A suitable example of a compliant balloon material is silicone that can safely withstand temperatures within the operating range of the body up to about 140°C. For example, the balloon material may be 40A silicone with a wall thickness of 0.0015 inches ± 0.001 inches formed in a diameter of 0.1 inches for reliable low-pressure inflation up to 12 mm in width. The balloon occluders are attached to the shaft 229 in an extended state (e.g., extended to twice the slack length) and both ends may be bonded with an adhesive such as cyanoacrylate. An optional heat-shrinkable collar (e.g., PET) may be added around the bonded ends of the balloon to increase strength. Any inflatable balloon occlusion of any embodiment disclosed herein may be somewhat spherical, such as the balloon 402 shown in Figure 14A, having a length 400 in the range of 5 mm to 30 mm (e.g., 12 mm) and a diameter 401 of similar dimensions in the range of 1 mm to 30 mm (e.g., 12 mm) when inflated outside the body. Alternatively, the inflatable balloon may be elongated or sausage-shaped, such as the balloon 403 shown in Figure 14B, having a length 404 in the range of 5 mm to 30 mm (e.g., 10 to 20 mm) and a smaller diameter 405 in the range of 1 mm to 30 mm (e.g., 4 mm to 20 mm, about 12 mm) when inflated outside the body. Compared to the spherical balloon 402, the elongated balloon 403 can provide a better fluid seal of the airway and can maintain its position better during use. However, as the balloon length increases, so does the friction between the balloon and the sheath, making delivery through the sheath more difficult or increasing the risk of damaging the balloon during delivery.Therefore, it would be preferable for the balloon to be 30 mm or less (for example, 25 mm or less, or 20 mm or less).

[0214] Alternatively, the inflatable balloon closure of any embodiment disclosed herein may also be a somewhat tapered balloon 408, such as the balloon 408 shown in Figure 14C, having, for example, a length 409 in the range of 5 mm to 30 mm and a first diameter 410 in the range of 1 mm to 30 mm (e.g., 12 mm) tapering to a second diameter 411 in the range of 0 mm to 20 mm (e.g., about 2 mm) when inflated outside the body, where the first diameter (i.e., the larger end of the tapered balloon 408) is further away from the ablation electrode than the second diameter. This tapered balloon shape allows for a functional seal of the airway while improving the ability of the airway and lung tissue to collapse toward the ablation electrode when a vacuum is applied to the airway during use.

[0215] Another alternative embodiment of the occluded balloon 423, as shown in Figure 14D, may have an elongated shape having a proximal portion 412, a distal portion 413, and a waist portion 414 between them. For example, when inflated outside the body, the proximal portion 412 of the balloon 423 may have a width 418 in the range of 1 mm to 30 mm (e.g., about 12 mm), the distal portion 413 may have a width 419 in the range of 1 mm to 20 mm (e.g., about 10 mm), and the waist portion 414 may have a width 421 less than the widths 418 and 419 in the range of 1 mm to 19 mm (e.g., about 8 mm). If necessary, the width 419 of the distal portion may be smaller than the width 418 of the proximal portion. One way to produce this shape of the balloon is to slightly thicken the balloon material in the waist portion 414. This balloon structure can close the airway and may be particularly beneficial when positioned near the opening of a target bronchus, where the proximal portion 412 is positioned to seal the opening of the target bronchus, while the distal portion 413 may be positioned within the target bronchus.

[0216] Alternatively, the occlusion balloon 231 may be a deployable valve having an occlusion material such as PTFE, or a deployable stent, or any other shape of occlusion structure.

[0217] Figure 4A shows an ablation device 220, shown in Figure 3, introduced into a selected airway 151, comprising an elongated shaft 229, a space closure plug (e.g., an occluder) 231 positioned distal to the shaft to occlude the airway, and at least one air removal port 235 that fluidly communicates with a lumen (not shown) that can be connected to a suction device (e.g., a vacuum pump) at the proximal end of the catheter to remove air from the airway 151 distal to the occluder 231 and collapse a target lung site, lung segment, or lobe. In an exemplary embodiment, the device 220 has four air removal ports 235, each having a diameter of 0.017 inches. Air may also be removed from the target lung site by applying negative pressure (e.g., using a suction device) to the lumen communicating with the air removal ports 235, which draws air from the lung site through the lumen to the proximal end of the device outside the patient. As shown, the air removal port 235 is identical to the port through which a conductive fluid (e.g., hypertonic saline) can be delivered. Alternatively, air may be removed from the target site of the lung by applying suction force to various lumens on the shaft 229, such as the guidewire lumen 236 having the distal exit port of the occluder 231 or an additional lumen (not shown). Alternative methods for at least partially collapsing the target site of the lung are described herein.

[0218] The apparatus 220 shown in Figures 3 and 4A further comprises a distal electrode 234 located in the distal portion 215 of the apparatus 220 and connected to a conductor 238 (e.g., 32AWG copper wire) passing through the apparatus shaft 229, to a proximal portion that can be connected to an energy transfer console for the transfer of RF ablation energy. Sufficient electrical insulation should be provided to insulate between the conductor and the electrode and avoid electrical stress. During the transfer of ablation energy, an RF voltage of 300V at a frequency in the range of 300kHz to 1MHz may be applied. The minimum dielectric strength may be about 2000V / mm. For example, the electrical insulation may be provided by insulation on the conductor and shaft material. Additionally, a dielectric material such as a UV-curing adhesive may be injected into the lumen in the shaft 229 supporting the conductor in at least the distal portion of the apparatus adjacent to the distal electrode 234 to improve the dielectric strength between the distal electrode 234 and the proximal electrode 237. The distal electrode 234 may be cylindrical in shape and have a diameter in the range of 0.5 mm to 2 mm (e.g., about 1.35 mm) and a length in the range of 3 to 20 mm (e.g., 3 mm to 10 mm, about 5 mm). Any proximal electrode 237 is positioned on the shaft 229 distal to the occlusion device 231 (e.g., in the range of 1 mm to 8 mm, at a distance of about 5 mm 239) and proximal to the distal electrode 234 (e.g., in the range of 5 to 15 mm, at a distance of about 10 mm 240). Any proximal electrode 237 may have a length in the range of 0.5 mm to 5 mm, preferably 1 mm ± 0.25 mm, and an outer diameter in the range of 0.5 mm to 2 mm (e.g., about 1.35 mm). The total distance 245 between the distal electrode 234 and the occlusion device 231 may be in the range of 1 mm to 40 mm (e.g., 5 mm to 30 mm, 10 mm to 20 mm, approximately 16 mm ± 2 mm), which may allow the distal electrode 234 to heat adjacent tissue and conductive fluid without risking thermal damage to the occlusion device 231, or avoid the risk of adversely affecting the occlusion device's ability to generate a fairly large ablation area 244 around the ablation electrode 234. The proximal electrode 237 is connected to a conductor 241 (e.g., 32AWG copper wire) that passes through the shaft 229 to the proximal end of a catheter that can be connected to an energy transfer console.If necessary, the distal electrode 234 and the proximal electrode 237 may be used together to complete an electrical circuit used to measure or monitor the electrical impedance or phase of tissue adjacent to the two electrodes. The impedance or phase may be used to assess the state of reduction in bronchial air volume during steps to reduce the air volume of a lung site or during the transfer of ablation energy, or to assess the degree of injection of conductive fluid into a target lung site, or to assess the degree of ablation of tissue adjacent to the electrodes. For example, in a bench test performed by bipolar impedance measured between the distal electrode 234 and the proximal electrode 237, it will decrease by approximately 5–20% (e.g., from approximately 400 Ω to approximately 350 Ω). Accordingly, the phase will increase from approximately the pre-collapse range of -20° to -60° to the post-collapse range of -10° to -30°. Figure 12 shows typical values ​​of impedance 300 and phase 301 at 480 kHz under various tissue contact conditions, including "standard tissue contact" and "strong tissue contact," following collapse of the target lung site and injection of "saline" into the target airway after hypertonic saline. Additionally, when the space within the collapsed airway is filled with hypertonic saline, the electrical impedance shows a constant and persistent decrease during the first part of the RF application. The constant and stable behavior of the electrical impedance may be used to indicate to the user that the target airway has collapsed, resulting in stronger tissue contact.

[0219] As shown in Figures 3 and 4A, the ablation catheter is equipped with an ablation electrode 234, the distal end of which is a short portion of the shaft having a guidewire port 236. Alternatively, the ablation catheter may be without a guidewire lumen. Furthermore, the ablation catheter may be without the short portion of the distal shaft of the ablation electrode 234, the catheter may be terminated at the ablation electrode, or it may have a hemispherical distal end.

[0220] Hypertonic saline (HTS) refers to all saline solutions with a sodium chloride (NaCl) concentration higher than physiologically normal (0.9%). Commonly used formulations contain 2%, 3%, 5%, 7%, and 23% NaCl and are generally available through hospital pharmacies in sterile bags or bottles. They are used in medical practice for their permeability rather than conductivity (e.g., to reduce edema). As mentioned above, other aqueous solutions (e.g., calcium chloride, magnesium chloride, sodium hydroxide, etc.) may also be used.

[0221] The conductive fluid (e.g., 3% to 30% hypertonic saline) may be delivered to the target lung site through the perfusion port 235 in the electrode 234, or additionally or alternatively, through an injection lumen (not shown) exiting the device 220 distal to the occluded balloon 231. The injection lumen may or may not exit through the port in the electrode. The injection lumen passes through the shaft 229 from the perfusion port (e.g., 235) to the proximal part of the device, which can be connected to the conductive fluid supply and, if necessary, a pump. Alternatively, a guidewire lumen 236 may be used to inject the conductive fluid.

[0222] Alternatively or additionally, in combination with collapsing a target site in the lung, a conductive fluid such as hypertonic saline may be injected into the already ventilated space. The use of hypertonic saline may enhance RF transmission based on a virtual electrode effect.

[0223] While the target lung site is occluded with the occluder 231, collapsed as necessary, and injected with conductive fluid, RF ablation energy may be transferred from the energy transfer console to the distal electrode 234. A temperature sensor 242 (e.g., a T-type thermocouple) may be located on or within the distal electrode 234 and may be connected to a thermocouple wire 243 passing through a shaft 229 to the proximal part of a device 220 connectable to the energy transfer console. The temperature sensor 242 may be used to monitor the temperature of the electrode 234 during energy transfer, where it is used as a parameter for controlling the energy transfer (e.g., temperature-controlled power supply so that the temperature matches a setpoint temperature in the range of 45°C to 115°C, preferably 50°C to 95°C, or constant-power controlled power supply at a maximum temperature in the range of 45°C to 115°C, preferably 50°C to 95°C, depending on specific local conditions to avoid overheating).

[0224] As shown in Figure 4A, the extent of ablation 244 is greatly influenced by the injection of conductive fluid into the target lung site.

[0225] The return electrode for completing the electrical circuit may be a dispersed electrode placed on the patient's skin, where RF energy is conducted through the tissue between the distal electrode 234 and the dispersed electrode. If necessary, or alternatively, a proximal electrode 237 may also be used to transmit ablation energy or to complete the electrical circuit (e.g., bipolar mode).

[0226] As shown in Figure 4A, a bronchoscope 221 having a lens 224 and a light source 223 is positioned in the patient's airway, and a catheter 220 configured for airway obstruction and tumor ablation is delivered through the working channel 225 of the bronchoscope to a target lung site 226 (e.g., lung site, lobe, or lung segment). The guidewire 227 may include a navigation sensor 228, or the distal end of the ablation catheter may include a navigation sensor 246 (see Figure 3) (e.g., virtual bronchoscopy, electromagnetic, 3D electromagnetic, ultrasonic) which can be positioned at the target location using a 3D navigation system, and the catheter 220 may advance via the guidewire through the guidewire lumen 236. If necessary, the catheter 220 may be retractable, allowing for adjustment of the distance from the occlusion device 231 to the distal electrode, and may comprise a first elongated shaft 229 having an occlusion balloon 231 attached to the distal end of a shaft 229 that is inflated by an injection fluid (e.g., air, sterile water, saline) passing through a lumen in a first shaft that is in fluid communication with a balloon inflation port 232 located inside the balloon. The first shaft 229 comprises a lumen 233 through which a second shaft 230, comprising at least one ablation electrode 234, can advance retractably. Alternatively, the ablation electrode may be positioned on the first shaft distal to the occlusion balloon at a fixed or adjustable distance between the balloon and the electrode, as shown in Figure 3. The retractable or adjustable distance between the balloon and the electrode can advantageously allow for the placement of the electrode near a tumor, the placement of the occlusion balloon at a desired location, which may depend on the shape of the airway, the size of the target lung site, or the size of the tumor. If necessary, the second shaft 230 may be directionally changeable or rotatable relative to the first shaft 229. The ablation electrode 234 may optionally have at least one perfusion port 235 for perfusing the electrode.

[0227] Alternatively or additionally, an optical fiber lens may be positioned distal to the occlusion structure on the elongated shaft 229, which may be used to visualize the airway distal to the occlusion structure. This can facilitate confirmation of, for example, airway constriction, electrode positioning, or airway damage while the occlusion structure is deployed.

[0228] If the electrodes are perfused by injecting fluid through port 235 as needed, the fluid may be drawn in by applying an attractive force to the guidewire lumen 236 to create a fluid flow.

[0229] An expandable occlusion element, such as the occlusion balloon 231 shown in Figure 4A, may be expanded to allow the catheter to be used in a range of airway sizes by expanding the occlusion element until it occludes the airway. Alternatively, if the target tumor is located in a narrow airway, the expandable occlusion element may be left unexpanded if it can fit into the narrow airway sufficiently to occlude it. In an alternative embodiment of the ablation catheter, as shown in Figure 4C, the catheter 600 may omit the expandable occlusion device, and the shaft 601 may be used to fit into and occlude the airway. If necessary, the ablation catheter 600 may have a tapered shaft portion 254 which is part of the distal portion of the catheter and is located proximal to the electrodes 237 and 234. The tapered shaft portion 254 can help seal the airway when advancing through an airway having a lumen diameter 603 less than or equal to the shaft diameter 602.

[0230] Alternatively, as shown in Figures 5A and 6A, the apparatus 420 may have two occlusion elements, such as an inflatable balloon or occlusion devices 431, 481. One occlusion element is located proximal to the ablation electrode, and the other is located distal to the electrode. The elongated shaft 429 is provided with two lumens 422, 483 (e.g., polyimide tubes with an inner diameter of 0.015 inches passing through the lumens in the shaft 429) having corresponding ports 432, 482 located within the occlusion devices 431, 481, for inflating and deflating the occlusion devices. The occlusion device 431 or 481 may be a balloon (e.g., a compliant balloon) of a size that occludes the airway or occludes a certain range of airway diameters (e.g., a diameter in the range of 3 mm to 10 mm). The distance between the distal and proximal occlusion devices is predetermined in this embodiment. For example, the distance between the balloons may be in the range of 20 mm to 40 mm. The occluders 431,481 may be inflated by an injection fluid (e.g., a gas such as air, water or saline solution, or a liquid such as a control solution) passing through lumens 422,483 and into the corresponding occluders 431,481. If necessary, the fluid may be injected manually using a syringe connected to the proximal part of the device 420, and the fluid pressure may be contained by closing a lockstop valve. The occluders may be deflated for removal by opening the lockstop valve and drawing the inflated fluid out of the balloon using a syringe. Alternatively, the system for operating the device may include a pump for injecting or removing fluid to inflate or deflate the balloons simultaneously or individually.

[0231] Alternatively, the occlusion balloon 431 or 481 may be any form of occlusion structure, such as a deployable valve or deployable stent having an occlusion material such as PTFE.

[0232] FIG. 6A shows an ablation device 420 introduced into a selected airway 151, comprising an elongated shaft 429, a proximal occluder 431 and a distal occluder 481, both disposed at the distal portion of the shaft for occluding the airway, proximal or distal to the electrodes respectively, and an air removal port 435 in fluid communication with a lumen (not shown) connectable at the proximal portion of the device to a suction device (e.g., a vacuum pump) for removing air from the airway region between the occluders 431, 481 to deflate a target lung site, lung region, or lobe. Air may be removed from the target lung site by applying a negative pressure to the lumen in communication with the air removal port 435 (e.g., using a suction device), which draws air from the lung site through the lumen to the proximal portion of the device outside the patient. As shown, the air removal port 435 is the same port through which a conductive fluid (e.g., hypertonic saline) can be delivered. Alternatively, air may be removed from the target site of the lung by applying a suction force to a different lumen, such as a guide wire lumen 436 or an additional lumen (not shown) having an exit port between the occluders 431, 481 on the shaft 429. Alternative methods of at least partially deflating the target site of the lung are described herein.

[0233] A conductive fluid (e.g., 5 - 30% hypertonic saline) may be delivered to the target lung site through the perfusion port 435 in the electrode 434 or, additionally or alternatively, through an infusion lumen (not shown) exiting the device 420 distal to the occlusion balloon 431. The infusion lumen may or may not exit through a port in the electrode. The infusion lumen passes through the shaft 429 from the perfusion port (e.g., 435) to the proximal portion of the device connectable to a conductive fluid supply and, optionally, a pump.

[0234] As shown in FIG. 6A, a bronchoscope 221 having a lens 224 and a light source 223 is disposed within a patient's airway, and a catheter 420 configured for airway occlusion and tumor ablation is delivered through a working channel 225 of the bronchoscope to a target lung site 226 (e.g., a lung site, lobe, or region). The guide wire 227 may include a navigation sensor 228, or the distal end of the ablation catheter may be provided with a navigation sensor 446 (e.g., virtual bronchoscopy, electromagnetic, 3D electromagnetic, ultrasonic) (of FIG. 5A) that can be positioned at the target location using a 3D navigation system, and the catheter 420 may advance through a guide wire passing through a guide wire lumen 436.

[0235] If desired, as shown in FIG. 5B, the catheter 520 may be telescopic such that the distance from the proximal occluder 531 to the distal electrode is adjustable (e.g., from a first distance in the range of 20 - 40 mm to a second distance in the range of 30 - 70 mm), and includes a first elongated shaft 529 having a proximal occlusion balloon 531 attached to the distal portion of a shaft 529 that is inflated by an infusion fluid (e.g., air, sterile water, saline) passing through a lumen 522 in a first shaft in fluid communication with a balloon inflation port 532 located inside the proximal balloon. The first shaft 529 includes a lumen 533, and a second shaft 230 having at least one ablation electrode 534 and a distal balloon 581 may telescopically advance together through the lumen 533.

[0236] The second shaft 230 includes a lumen 583 (e.g., a 0.015 - inch inner diameter polyimide tube passing through the lumen within the second shaft 230) having a corresponding port 582 disposed within the occluder 581 for inflating and deflating the occluder. The occluder 581 may be a balloon (e.g., a compliant balloon) sized to occlude the airway or to occlude a range of airway diameters (e.g., diameters in the range of 3 - 10 mm).

[0237] Figure 6B shows an ablation device 520, shown in Figure 5B, introduced into a selected airway 151, comprising an elongated first shaft 529 and a second shaft 230, a proximal occluder 531 and a distal occluder 581 proximal or distal to the electrodes, respectively, and an air removal port 535 that fluidically communicates with a lumen (not shown) connectable to a suction device (e.g., a vacuum pump) at the proximal end of the device, for removing air from the airway area between the occluders 531, 581 and collapsing a target lung site, lung segment, or lobe. Air may also be removed from the target lung site by applying negative pressure (e.g., using a suction device) to the lumen communicating with the air removal port 535, thereby drawing air from the lung site through the lumen to the proximal end of the device outside the patient. As shown, the air removal port 535 is identical to a port through which a conductive fluid (e.g., hypertonic saline) can be delivered. Alternatively, air may be removed from the target site of the lung by applying suction force to another lumen, such as a guidewire lumen 536 or an additional lumen (not shown), having an exit port between the occluders 531, 581, on the second shaft 230. Alternative methods for at least partially collapsing the target site of the lung are described herein.

[0238] A conductive fluid (e.g., 5-30% hypertonic saline) may be delivered to the target lung site through a perfusion port 535 in the electrode 534, or additionally or alternatively, through an injection lumen (not shown) exiting from the device 520 distal to the occluded balloon 531. The injection lumen may or may not exit through a port in the electrode. The injection lumen passes through the second shaft 230 from the perfusion port (e.g., 535) to the proximal part of the device, which can be connected to a conductive fluid supply and, if necessary, a pump.

[0239] The expandable or adjustable distance between the proximal balloon and the electrode, or between the proximal balloon and the distal balloon, can advantageously allow for the placement of the electrode near the tumor, or the placement of the occlusion balloon at a desired location, which may depend on the shape of the airway, the size of the target lung site, or the size of the tumor. In particular, the adjustable distance between the proximal and distal occlusion devices allows for the isolation of more specific areas of the airway, which would significantly reduce or minimize the risks or undesirable effects associated with the procedure, such as exhaustion, fluid infusion, or ablation. If necessary, the second shaft 230 may be directional or rotatable relative to the first shaft 529. The ablation electrode 534 may optionally have at least one perfusion port 535 for perfusing the electrode.

[0240] The double occlusion device structure can offer several additional advantages, such as the following: • Reduction of the effects of collateral ventilation. Collateral ventilation is a normal physiological function of the lungs. During collateral ventilation, air can move between lobes, bronchioles, or alveoli through interbronchiolar pathways within the lungs. Although the airflow during collateral ventilation is smaller than that of normal breathing, it can still significantly affect local air removal or fluid infusion. A double occlusion device structure can create a more isolated space within the target airway. In such an isolated airway region, the effects of collateral ventilation can be minimized. • More focused treatment of local areas. In isolated airway areas, air expulsion and conductive fluid injection can be applied to this specific location, and ablation energy can be more concentrated at this location. The occlusion device can act as an object blocker or energy sealant, reducing the effects of diffusion of air, fluid, or energy, and thus saving energy. • Reduction of the risk of generating undesirable damage to pleural tissue. A double occlusion device structure can provide additional fixation points to further stabilize the ablation catheter. In particular, the distal portion of the ablation catheter, which has the tip of the ablation electrode, ablation needle, or guidewire, can be freely deformed or tilted within the catheter's initial strength limits. Accidental movement of the distal portion of the catheter, e.g., elongation of the shaft due to uneven passive forces during air venting or fluid injection, and movement of the distal end, can all cause undesirable damage to pleural tissue (e.g., perforation, friction or granulation, tissue deformation), affecting the ablation outcome and leading to further intervention or treatment. Furthermore, it may be desirable to avoid delivering hypertonic saline or heat to the pleura or the lung parenchyma immediately adjacent to the pleura. A distal occlusion balloon can reduce the risk of pleural damage through thermal energy or dehydration by hypertonic saline by keeping the injected hypertonic saline at a safe distance from the pleura. For example, the distal occlusion balloon may have a length of at least 10 mm, which is expected to be a safe distance from the pleura. When the distal end of the device is inserted to the distal end of the airway, which may be within 10 mm of the pleura, and the distal occlusion balloon is inflated, the injection of hypertonic saline and heat transfer can be expected to maintain a safe distance from the pleura.

[0241] A method of ablating lung tumor cells may be carried out by isolating a target site in the lung near the tumor cells using the ablation catheter described above, delivering hypertonic saline (HTS) to the isolated site in the lung, and applying heat to the isolated site in the lung. The HTS may have a sodium (NaCl) concentration of at least 3% w / v (e.g., in the range of 3% to 30% w / v, or 5% to 25% w / v).

[0242] The HTS may be heated to a range of 60–115°C within the target site in the lung. Heat may be applied by transmitting radio frequency (RF) current from an RF electrode on a catheter to the HTS solution injected into the natural airway of the lung near the lung tumor. The target site in the lung may be exposed to heat and HTS for a duration ranging from 30 seconds to 30 minutes (e.g., 1–30 minutes, 1–15 minutes, 2–10 minutes).

[0243] The application of RF energy to liquids efficiently utilizes the liquid as a virtual electrode to transfer energy in order to ablate tumor cells. The HTS solution conducts RF energy into the lung tissue, causing tissue heating. Additionally, some of the RF energy heats the liquid, allowing it to ablate tumor cells.

[0244] The target site in the lung is isolated by inflating a first occlusion balloon within the natural airway, where the balloon is proximal to the target site in the lung. Furthermore, a second (distal) occlusion balloon within the airway distal to the ablation electrode may also be used to occlude the airway. One or both balloons occlude the natural airway, forming a portion of the airway into which the HTS solution is injected, and restricting the flow of fluid outside that portion of the airway.

[0245] Alternatively or additionally, an optical fiber lens may be positioned distal to the proximal occlusion structure on the first elongated shaft 529, and another lens may be positioned distal to the distal occlusion structure on the second shaft 230, which may be used to visualize the airway distal to the selected occlusion structure. This also facilitates, for example, confirmation of airway constriction, electrode position, or airway damage while the occlusion structure is deployed.

[0246] Alternatively or additionally, a lung site may be collapsed by causing a limited and controlled pneumothorax by placing a needle into the pleural cavity (e.g., the pleural sinus), which may facilitate the collapse of the target lung site. Thoracentesis (also known as pleural tap) is a well-known procedure for removing fluid or air from around the lung by inserting a needle through the chest wall into the pleural cavity. This may also be done by altering the pressure difference between the pleural cavity and the lung site, making it easier to collapse the target lung site. If necessary, a dispersed return electrode may be inserted through thoracentesis and placed in the lung to preferentially direct the RF current to the return electrode. If necessary, thoracentesis may be used to deliver a cryogenic fluid, such as saline or sterile water, to a thermally protected area from ablation, particularly when the tumor is in the periphery of the lung and there is a risk of ablating the visceral pleura or internal organs such as the heart, esophagus, nerves, diaphragm, or other non-critical target tissues.

[0247] If necessary, any occluded balloon may have a micropatterned surface on its outer surface where the balloon is intended to contact the airway wall. The micropatterned surface may be molded into the balloon material and may have a hydrophilic surface that increases surface moisture tension, resulting in a higher retention force that improves the occluded balloon's ability to maintain its fixed position. This improved retention force may also reduce the risk of fluid leakage as it passes through the balloon. The micropattern may have multiple columns with height and width dimensions of less than 1000 nanometers. For example, the micropattern may be molded into a thin film using techniques well known in the art (e.g., US8720047, transferred to Hoowaki, LLC).

[0248] [Embodiment #2 (Needle electrode for puncturing tissue and placing it in a tumor or lung parenchyma)]

[0249] Alternatively, as shown in Figures 7 and 8, at least one RF electrode 234 in the embodiment shown in Figure 3 or 4A may be at least one needle electrode 250 used to puncture through the airway wall or through the tumor in order to position the RF electrode 250 within the target tumor 80 or within the lung parenchyma near the tumor. The needle electrode 250 may have a perfusion port 251 that is in fluid communication with a perfusion lumen that passes through the shaft 229 to the proximal end of the catheter. The needle electrode 250 may have a length in the range of 3 to 20 mm (e.g., 5 to 15 mm, about 7 mm) and a diameter in the range of 0.5 mm to 2 mm (e.g., about 1.35 mm). If necessary, the needle electrode may include a guidewire lumen 252 (e.g., having an inner diameter of 0.015 inches to 0.030 inches) that allows the device to be delivered on a guidewire 228. The tip 253 of the needle electrode 250 may be sharpened to allow puncture through the airway wall or tumor, for example, the tip 253 may be beveled as shown, or may have another sharp contour such as the tip of a pencil. During use, as shown in Figure 8, when the needle electrode 250 is placed in the parenchyma or tumor, a conductive fluid (e.g., 5-30% hypertonic saline) may be injected into the lung parenchyma or tumor through the perfusion port 251.

[0250] If necessary, the device 225 may be transported after the biopsy on a guidewire placed in the lung parenchyma or tumor, thereby allowing the needle electrode 250 to be easily positioned in the same location from which the specimen was collected.

[0251] If necessary, the distal portion 256 of the device 255 having the needle electrode 250 may have a spring-loading mechanism comprising a spring 257 and an engagement lock 258 that holds the needle electrode 250 in a first spring-loaded position. When the lock 258 is released by an actuator on the proximal portion of the device 255, the spring 257 presses against the shaft 259 to which the needle electrode 250 is attached, extending the distance 260 from a spring-loaded state (e.g., 5-10 mm) to an unloaded state (e.g., an increase of 5-15 mm). The thrust force provided by releasing the spring-loading mechanism can facilitate puncture of the airway wall by the needle electrode 250. The engagement lock 258 may be a mechanical mechanism such as a rotating lever that engages with an element firmly connected to the distal shaft 259. The rotating lever may be connected to a pull wire 261, which passes through the device shaft 229 to a proximal part of the device that can be connected to an actuator that can be used to apply tension to the pull wire to release the locking mechanism 258.

[0252] In an alternative embodiment of lung cancer ablation, a catheter that can be punctured through the airway wall may have an RF puncture electrode at its tip (e.g., 0.5 mm in diameter and 1 mm in length), and the outer diameter of the shaft may taper from the RF puncture electrode diameter to the distal ablation electrode diameter (e.g., about 1.5 mm). The RF puncture electrode may be connectable to an energy delivery console having an RF puncture mode. RF puncture electrodes and energy delivery profiles are well known, for example, in the field of cardiac surgery such as septal puncture.

[0253] If necessary, the distal end of the device having the needle electrode may be directional, which may facilitate directing the sharp tip of the needle electrode 250 towards the airway wall in order to puncture through the wall or into the tumor and place the needle electrode 250 in the lung parenchyma near or within the lung tumor, or inside the tumor itself.

[0254] If desired, the proximal electrode 237 may be used to transmit ablation RF energy in addition to, instead of, or in cooperation with the distal electrode 250. The proximal electrode 237 may optionally have a perfusion port 263 that is in fluid communication with a perfusion lumen (not shown) that passes through the shaft 229 to the proximal portion of the device 255, and the perfusion lumen may be connectable to a conductive fluid source or pump at the proximal portion of the device. The perfusion ports 263 and 251 on the proximal electrode 237 and the distal electrode 250 may be connected to the same perfusion lumen or individual lumens for delivering the conductive fluid. In an embodiment having a perfusion port 263 on the proximal electrode 237 as well as the perfusion port 251 on the distal needle electrode 250, as shown in FIG. 8, the conductive fluid may be delivered into the lung parenchyma or tumor and / or into the airways distal to the occluder 231 from either or preferably both of the ports 251 or 263. Preferably, the RF energy may be transmitted to the two electrodes 237 and 250 in a dual-channel monopolar RF mode. For example, each channel may have a circuit completed using a dispersive electrode on the patient's skin or in the body, and the channels may be floating relative to each other. Alternatively, the ablation energy console may transmit RF energy to the two electrodes 250 and 237 in a bipolar mode.

[0255] [Embodiment #3 (Ablation Electrodes on Multiple Shafts)]

[0256] Figure 9 shows two catheters 100 and 101 having energy transfer electrodes 102 and 103. The two catheters 100 and 101 are introduced individually using a flexible bronchoscope 221, and are shown as an example in which the electrodes are positioned to terminate in two separate airways on two sides of the target tumor 80. The apparatus may also include an occlusion catheter 270 which can be delivered through the working channel 225 of the bronchoscope 221 or, if necessary, through a delivery sheath 213. The occlusion catheter 270 may also include an occlusion device 271, such as a compliant balloon, attached to the shaft of the occlusion catheter 270. An inflation lumen passes through the occlusion catheter shaft and exits through a port 272 in the occlusion device for deploying or inflating the occlusion device 271. The shaft of the occlusion catheter 270 may also include two or more ablation catheter lumens 273 and 274 that exit the shaft distal to the occlusion device 271. Alternative forms of the occlusion elements may be envisioned as disclosed herein. Catheters 100 and 101 may be delivered to the distal airway of the occlusion device through lumens 273 and 274. Lumens 273 and 274 may each be equipped with valves that seal around the delivered catheters 100 and 101 to contain low pressure or conductive fluid within a target area of ​​the lung site. Catheters may be delivered on a guidewire 104 via guidewire lumens 106 and 107. Electrodes may be connected to conductors that pass through the catheter shaft to the proximal end of the catheter and terminate, for example, in an electrical connector, which may be electrically connected to an RF generator, for example, using a connector cable. Each catheter may incorporate one or more electrodes that can be energized together or individually. If necessary, each catheter may be equipped with impedance and phase monitoring electrodes 275 and 276 for monitoring tissue impedance and the phase between the distal electrode 103 and the impedance electrode 276, or between the distal electrode 102 and the impedance electrode 275, in order to evaluate airway collapse, injection of conductive fluid, tissue characteristics, or the degree of tissue ablation.The conductive fluid 216 may be injected into the target lung area occluded by the occluding device 271 through the perfusion ports 277 or 278 of the electrodes 102 and 103.

[0257] The electrodes of the catheter may be positioned at a desired location within the airway by delivering catheters 100 and 101 via a guidewire 104, for example, placed using an ultrathin bronchoscope. Catheters 100 and 101 may be equipped with guidewire lumens 106 and 107, and over-the-wire (OTW) exchange may be employed. Currently available devices may be used to navigate to a desired location within the patient's airway. For example, electromagnetic navigation bronchoscopy is a medical procedure that utilizes electromagnetic technology designed to locate and guide endoscopic tools or catheters through the bronchial pathways of the lung. Virtual bronchoscopy (VB) is a three-dimensional computer-generated technique that generates images of the bronchi from spiral CT data. Using a virtual three-dimensional bronchial map from recent computed tomography (CT) chest scans and a disposable catheter set, a physician may navigate to a desired location within the lung, a biopsy lesion, take samples from lymph nodes, guide a radiotherapy catheter, or insert markers to guide a brachytherapy catheter. Such existing techniques may be used for procedure planning, tumor diagnosis by biopsy, and placement of guidewires for positioning one or more therapeutic catheters. After the guidewire 104 is placed in the airway adjacent to the target ablation area (e.g., within 0–10 mm of the target ablation area, or within the target ablation area), the ultrathin bronchoscope can be withdrawn, leaving the wire in the appropriate position, and the electrode catheter may be replaced via the wire. Alternatively, electromagnetic navigation bronchoscopy may be used with similar results. If necessary, multiple catheters may alternatively have a double-balloon structure, similar to the device shown in Figure 5A or 5B.

[0258] Multiple catheters equipped with electrodes or balloon elements may be placed in the manner described by replacing a bronchoscope with the catheters via a wire. After the tumor is therefore surrounded by the energy delivery elements and the bronchoscope and guidewire are removed, the proximal end of the catheter may be connected to an extracorporeal RF generator. If biopsy results indicate lymph node metastasis, the technical subject matter of this disclosure may also be used to ablate the lymph nodes.

[0259] Radiopaque markers on the guidewire or catheter may be used to precisely position the electrode in the desired location. For example, the RF electrode may be radiopaque. Any ablation catheter disclosed herein may be provided with a retention or fixation mechanism distal to the catheter to ensure that its energy delivery element is placed in the desired location and to prevent accidental dislodgement, particularly when the patient breathes or coughs. For example, the retention or fixation mechanism may include a portion of the catheter that employs a predetermined non-linear shape (not shown), an inflatable balloon, a spring load or wire-actuated spline, a stent, or a deployable barb (i.e., a return) positioned on the distal portion of the catheter. The size and design of the electrode catheter may be made to fit the working channel of a standard or ultrathin bronchoscope. Multiple electrical connections for energy transfer and signal transmission (temperature and impedance) are envisioned. The ablation catheter may be provided with a material delivery lumen, which may be used to deliver materials into the airway, such as drugs, contrast agents for visualizing biological structures using fluoroscopy, and substances that induce lung collapse. If necessary, the guidewire lumen may function as a material delivery lumen when the guidewire is removed, which may allow for minimizing the catheter diameter. The ablation catheter may also include a perfusion delivery lumen used to inject perfusion fluid into the airway surrounding the electrode to prevent charring and impedance increases and to allow for greater damage generation. The perfusion delivery lumen may be the same lumen as the material delivery lumen or the guidewire lumen.

[0260] As shown in Figure 10A, three RF electrodes, named E1, E2, and E3, are positioned in three separate airways, named B1, B2, and B3. For example, the three electrodes may be delivered on individual catheters, as in the catheter embodiment shown in Figure 9. A multiphase RF ablation waveform may be used to establish a rotational ablation field, which delivers ablation energy to the tumor in a more localized modality. Figure 10B shows a multiphase RF waveform that may be used to ablate a target tumor surrounded by multiple RF electrodes, where RF1 is the RF signal delivered to electrode E1, RF2 is delivered to electrode E2, and RF3 is delivered to electrode E3. In this example, the waveforms RF1, RF2, and RF3 are phase-shifted by 120°. Applying such phase-shifted waveforms generates a rotational multipolar ablation field, which has the potential to improve coverage of the tumor space and result in more uniform damage. In principle, phase-difference RF ablation functions similarly to bipolar ablation, except that the current from or to a series of electrodes is affected by the phase difference. Each electrode is driven by an RF source having a different phase. The RF voltage generated between each pair of electrodes (e.g., E1 and E2, E2 and E3, and E3 and E1) causes the RF current to flow into the tumor space in a more uniform heating pattern. The power level is in the range of 1 to 200 W for a duration of 30 seconds to 30 minutes. A temperature sensor may be employed to control a local temperature value around a user-defined target. The temperature of such a target can vary in the range of 60 to 115°C, preferably 50 to 80°C. The RF generator capable of delivering phase-difference ablation energy may have an additional RF output stage. Figure 10C shows an example of a multiphase RF energy supply unit 175 having independently controlled phases for each output 177. The phase of the RF signal at each output may be controlled via software or in hardware by individual RF power supply units 176, or alternatively by a central microcontroller, for example by splitting a higher frequency digital clock, as shown in Figure 10D.As shown in Figure 10D, the digital clock may include a fundamental frequency 180 having a period (e.g., t0 to t1) that is one-sixth of the period of frequencies 181, 182, and 183, which is transmitted to the ablation electrodes and shifted by one fundamental frequency. If necessary, each electrode E1, E2, and E3 (and their respective RF output voltages VRF1, VRF2, and VRF3) may complete the electrical circuit using a distributed grounding pad connected to the ground voltage VGND at terminal 178 of the RF energy supply unit 175. Alternative embodiments may have more than three electrodes and waveforms, or fewer than three (e.g., two electrodes and waveforms).

[0261] Examples of bipolar or multipolar RF ablation parameters delivered by the RF console to multiple electrodes, multiple balloons, or combinations of balloons and electrode energy elements may include a duration of 30 seconds to 30 minutes and a power range of 1 to 200 W. If high impedance (e.g., above 1000 ohms) is detected, the tissue impedance is expected to be in the range of 30 to 1000 ohms to avoid overheating, tissue burning due to poor contact between the electrodes and the airway wall, or uncontrolled ablation, and the system may terminate or reduce the power supply. After drying, the tissue is naturally or perfused with moisture, and energy delivery may automatically resume. Impedance monitoring may be used during energy delivery to determine whether the tissue temperature has risen sufficiently for effective tumor ablation, and may also trigger the termination of energy delivery. The parameters may be used in multiphase or single-phase RF ablation waveforms.

[0262] If necessary, the ablation energy console may deliver ablation energy in multi-channel monopolar mode to multiple RF electrodes (e.g., on a single ablation device or on separate ablation devices), and the independent waveforms (e.g., VRF1, VRF2 shown in Figure 10C) may be in phase.

[0263] [system]

[0264] Apparatus for intrabronchial lung tumor ablation as disclosed herein (e.g., apparatus 220, 255, or 270) may be part of a system 290 as shown in Figure 11, which further comprises a computer-controlled ablation energy (e.g., RF) console 291 with a programmable controller having software 292, a conductive fluid supply unit 293 and pump 294, a vacuum pump 295, an occlusion device inflator 296 (e.g., an inhaler, a syringe with a valve 297, an electric pump, an electric valve for pressurized fluid), and associated connector cables and tubing for connecting the proximal part of the apparatus to the console, pump, or vacuum pump.

[0265] If necessary, system 290 may comprise more than one ablation device, such as a plurality of ablation devices 100 and 101, or a plurality of ablation devices such as 220 or 255, which can be delivered through an occlusive catheter 270 as shown in Figure 9. System 290 may also comprise a guidewire 227, a delivery sheath 213, a dispersive grounding pad, or a bronchoscope 221. The ablation console 291 may further comprise an impedance and phase monitoring circuit and software 298, which can be connected to electrodes on the ablation devices (220, 255, 270) to measure impedance and phase and display those values ​​to the user. If necessary, the impedance and phase monitoring circuit and software 298 may be in a separate component which may be connected to the ablation console to input the measured impedance and phase and control the algorithm of the ablation console software 292.

[0266] The system may include an ablation console 291, a pump 294, controller software 292, and optionally an impedance and phase monitoring circuit and software 298, or any combination thereof. Furthermore, the ablation console 291, pump 294, controller software 292, and optionally an impedance and phase monitoring circuit and software 298 may be provided separately.

[0267] Software 292 may include an algorithm to control a vacuum pump 295 to remove air from a target lung site. The vacuum pump may be equipped with a pressure sensor indicating the pressure difference between the atmosphere and the target lung site. The vacuum pump may apply a maximum negative pressure difference in the range of 1 to 5 atm, and the algorithm may input the negative pressure difference and stop the vacuum pump when the pressure difference reaches the maximum negative pressure difference, at which point the vacuum pump may be signaled to block the airflow from the lung site and maintain pressure in the lung, for example by closing a valve. In embodiments, a conductive fluid is injected through the same lumen through which air is removed from the lung, and the system may be equipped with an automatic control switching valve that switches fluid communication from the vacuum pump to the injection pump once the algorithm detects sufficient collapse of the lung site via either pressure sensor signals or tissue impedance and phase associated with distal and proximal electrodes on the device (e.g., 220, 255, or 270). For example, software 292 may control the ablation console 291 to transmit electrical waveforms (e.g., low-power high-frequency currents across frequency bands) to distal and proximal electrodes to monitor tissue impedance or phase while the vacuum pump 295 is operating and to control the vacuum pump to stop when a drop in impedance indicates lung collapse. Software 292 may also control the pump 294 to deliver conductive fluid from the fluid supply unit 293 to the device and to the target lung site, and may transmit electrical waveforms to simultaneously monitor impedance or phase to evaluate the infusion, if necessary. If necessary, the infusion may continue (e.g., at a rate of about 5 mL / min) while ablation energy is being delivered from the console 291. Software 292 may further control the ablation energy delivery profile, including safe monitoring of temperature and impedance.

[0268] Alternatively, negative pressure may be manually applied to remove air from the target lung site by drawing air through the catheter (e.g., through the perfusion port 235 and perfusion lumen) using a manual suction device. The manual suction device may be a syringe and may further have two check valves that allow air to be drawn out of the catheter when the syringe is pulled and released into the atmosphere when the syringe is pushed. A pressure sensor may be placed in the perfusion lumen. During use, the physician may manually apply suction force to the manual suction device while positioning the ablation catheter in the patient's lung, deploying the occlusion device, and then applying a low current and monitoring the bipolar impedance, measured by measuring the tissue impedance between the proximal and distal electrodes, and the pressure, measured optionally by a pressure sensor. A 5%–20% drop in impedance may indicate that the airway has collapsed sufficiently to proceed. Following the application of suction force and confirmation of sufficient collapse via impedance or pressure drop, the user may hold the suction device stationary while monitoring the impedance or pressure. A stable impedance or pressure may indicate that the target lung site remains sufficiently collapsed. An increase in impedance or pressure during this stage may indicate that the occluder is not sufficiently occluding the airway, which the user may correct by repositioning, inspecting, or reinflating the occluder.

[0269] If the suction force is applied manually, the user may initiate the algorithm (for example, by pressing an actuator on the ablation console) if they are satisfied that the target lung site has been sufficiently collapsed. If the suction force is applied automatically by the software 292 algorithm, the algorithm may send a message to the user indicating that the decrease in impedance or pressure during the suction phase is sufficient to proceed with ablation, and the user may initiate the ablation phase (for example, by pressing an actuator on the ablation console) which allows the algorithm to continue.

[0270] The algorithm of software 292 may manage the flow rate of the conductive fluid being injected by controlling the pump speed. During the ablation phase, the algorithm of software 292 may enter a preparatory phase instructing pump 294 to deliver conductive fluid from conductive fluid source 293 without delivering ablation RF energy, in order to prepare the conductive fluid in the injection lumen and to ensure that at least a small amount of conductive fluid is in the airway of the target lung site before ablationable RF energy begins to be delivered. For example, the preparatory phase may include injecting conductive fluid at a rate of 5 mL / min for 5 seconds, or up to a maximum duration (e.g., 15 seconds), until the measured impedance drops by a further 10% to 20%. A drop of at least 10% in impedance may indicate that the perfusion is functioning properly. If the impedance does not drop during this preparatory phase, the algorithm may send an error message to the user indicating a problem that may occur related to the perfusion, fluid pump, or conductive fluid supply. If an impedance drop (e.g., a value in the range of 10% to 20%) is measured during the preparation phase, the algorithm may proceed to the ablation RF transmission phase.

[0271] In one embodiment, during the ablation RF transmission phase, when the ablation RF begins to be transmitted, the rate of perfusion of conductive fluid may start at 0 mL / min. This may help minimize the amount of conductive fluid delivered. During the transmission of ablation RF, the temperature monitored by the ablation electrodes 234, 434, 534, 250 and associated temperature sensors 242, 442, 542, 262 may be input to a control algorithm, and when the temperature rises to a predetermined upper threshold temperature (e.g., 95°C), the perfusion flow may be started (e.g., at a rate of 5 mL / min) while the transmission of RF energy continues at a constant power. The perfusion is expected to cool the ablation electrodes so that they remain below the upper temperature threshold. If the measured temperature drops to a predetermined lower threshold (e.g., 85°C), the perfusion flow may be commanded to stop or decrease while maintaining a constant RF electrode temperature, which may allow the temperature to rise. The algorithm may continue to adjust the flow rate to maintain the temperature within the upper and lower thresholds until a pre-set ablation duration is reached or another termination trigger occurs. Other termination triggers may include manual termination of ablation by the user by pressing the ablation RF power actuator, or an automatic termination error caused by the algorithm. An automatic termination error may be caused by the inability to maintain the temperature within the upper and lower thresholds, or by a system component failure (e.g., insufficient supply of conductive fluid, pump failure, valve failure).

[0272] The ablation duration may range from 30 seconds to 30 minutes and may be selected by the physician based on the desired ablation size, if necessary. For example, using animal and bench models, the authors have experimentally demonstrated that a 5-minute ablation with 5% HTS along with a 5 mm long and 1.5 mm diameter ablation electrode 234 produces a spherical ablation of approximately 1.5–2 cm in diameter, at least 7 minutes produces an ablation of 2–2.5 cm in diameter, at least 10 minutes produces an ablation of 2.5–3 cm, and at least 15 minutes produces an ablation of 3 cm or larger in diameter. Depending on the size of the tumor and its location relative to the target airway, the physician may select an appropriate ablation duration to encircle the tumor, or may input the duration into the algorithm using the user interface on the console 291. The algorithm may display the selected duration and the estimated ablation diameter according to the input duration on the user interface. Alternatively, the physician may input the desired ablation dimension (e.g., diameter) into the algorithm, and the duration may be calculated and displayed. The physician may develop a treatment plan depending on the size and location of the target tumor. The treatment plan may include the desired ablation size and location within the airway relative to the tumor, and, if necessary, may include multiple ablations from various target locations within the lung to ablate the tumor from multiple directions if it is estimated that a single ablation will not completely encircle the tumor.

[0273] If necessary, following the termination of ablation RF transmission (e.g., completion of the ablation duration or early termination of ablation), an algorithm may initiate suction to remove the injected conductive fluid.

[0274] Alternatively, software 292 may control the amount of conductive fluid delivered during the transfer of ablation energy (e.g., via pump speed) based on electrode temperature feedback from temperature sensors (e.g., 242, 262) to obtain a temperature setpoint. For example, a constant power may be delivered, or a constant injection flow rate may be delivered, and as the temperature setpoint is approached, the power, flow rate, or a combination of both may be gradually increased to achieve the temperature setpoint. If the actual electrode temperature is below the setpoint, the injection rate may be decreased and / or the power may be increased. If the actual electrode temperature is above the setpoint, the injection rate may be increased and / or the power may be decreased.

[0275] If necessary, the occluder inflation pressure may be monitored by a pressure sensor 425 located in the occluder inflation lumen between the occluder inflator 296 or valve 297 and the occluders 231, 431, 481, 531, 581. The occluder inflation pressure may be input and monitored by a software algorithm 292, which may be used by the algorithm to display the pressure on the user interface, for example, as a requirement for initiating vacuum suction (e.g., the balloon inflation pressure may need to exceed a predetermined threshold such as 2 atoms) or as a detection of a failure mode (e.g., a sudden drop in balloon inflation pressure may indicate rupture of an occluder, which may cause termination of RF transmission).

[0276] Conductive fluids such as hypertonic saline may have boiling points higher than 100°C, which means that higher fluid temperatures not only facilitate ablation of target tissue but also allow greater ablation energy to accumulate in the conductive fluid. This is particularly beneficial when heat and electrical energy are transferred through the cartilaginous airway walls to ablate tumors, as airway walls have relatively low thermal and electrical conductivity, and tumor ablation requires greater ablation. For example, conductive fluids such as 20% hypertonic saline may have boiling points in the range of approximately 105°C to 110°C.

[0277] Generating vapor within the target site of the occluded lung by increasing the temperature of the conductive fluid injected into the target site near its boiling point can be advantageous. Generating and confining vapor within the target site of the lung using an occlusion device (e.g., a balloon) can increase the vapor pressure of the conductive fluid, thereby further raising its boiling point, which may allow for the transfer of greater ablation energy. Exposing cartilaginous airway walls to a temperature of approximately 100°C for an extended period, for example, 2 to 10 minutes, has the advantage of softening their hardness, allowing the conductive fluid to penetrate better and advance toward the target lung tissue. Furthermore, when the lung parenchyma is heated, it contracts, and the airways connected to the parenchyma are pulled together closer. The vapor generated at the target lung site can move toward the relevant parenchyma and contract it before or during the transfer of ablation energy, which may improve the effectiveness of tumor ablation. The energy transfer console may have an energy transfer control algorithm that allows for temperature setpoints in a range close to the boiling point of the conductive fluid at the fluid pressure within the target site. If necessary, the algorithm may have a vapor generation phase in which energy is transferred at a temperature setpoint appropriate for vapor generation (for example, if 20% hypertonic saline is the conductive fluid, the temperature setpoint for the vapor generation phase may be in the range of 100°C to 110°C, preferably about 105°C). Ablation of the target lung tissue may be performed at such an elevated temperature setpoint and last for a duration of 1 to 10 minutes. Alternatively, the vapor generation phase may have a predetermined duration (e.g., up to 2 minutes) or may be controlled by monitoring the impedance between electrodes, where a sharp rise in high impedance may indicate vapor generation. Further alternatively, the vapor generation phase may be alternated with an ablation phase at a lower temperature setpoint. For example, energy transfer may be performed for the first 2 minutes at a 105°C setpoint, the next 2 minutes at an 85°C setpoint, the next 2 minutes at a 105°C setpoint, and so on, until the ablation duration (e.g., in the range of 8 to 15 minutes, or a total duration of about 10 minutes) is completed or the therapeutic objective is achieved (e.g., the moving average impedance exceeds the target threshold).If necessary, a pressure sensor on the distal end of the device may be used to input a pressure signal to a controller, and an increase in pressure may indicate sufficient steam generation. If necessary, the steam generation stage may cause heating of the conductive fluid by transferring ablation energy from an ablation element, or alternatively by transferring thermal energy from a direct heating resistance coil located on the device distal to the occlusion device. The direct heating resistance coil may be an electrically resistant metal having an electrical insulator (e.g., polyimide, parylene) spirally wound around the shaft of the device, which heats the conductive fluid solely by thermal conduction. As described above, the steam generation stage may be followed by a tumor ablation stage which may have a temperature setpoint lower than the temperature setpoint of the steam generation stage.

[0278] When the conductive fluid is injected into the target site, the control algorithm may use a target setting temperature in the range of 85°C to 115°C, preferably 90°C to 105°C, to keep the temperature below the boiling point of the conductive fluid. Alternatively, it would be desirable to generate vapor at the blocked target site if the setting temperature is in the range of 105°C to 115°C, provided that sufficient safety mechanisms are designed into the system, such as the immediate cessation of RF energy caused by a sudden change in impedance, temperature, or electrical phase (i.e., the phase between the ablation current and the ablation voltage).

[0279] As described herein, electrical impedance and phase may be measured between the proximal and distal electrodes, or between either of these electrodes and a dispersed electrode (e.g., a grounding pad placed on the skin). Impedance spectroscopy may be calculated by a software algorithm in the ablation console 291 to characterize the tissue near the impedance monitoring electrode through which current is transmitted. The tissue may be characterized to identify cancerous tissue by comparison with ablated cancerous tissue compared to normal tissue. Optionally, or alternatively, as shown in Figure 15, the ablation catheter may include a third electrode 537 located distal to the ablation electrode 234 in addition to the proximal electrode 237. Other components of the apparatus may be similar to those of the embodiment shown in Figure 3, with the call numbers remaining the same as in Figure 3, except for the third electrode 537. In Figure 15, the proximal electrode 237 may be positioned on the second side (e.g., proximal side) of the tumor 80, while the third electrode 537 may be positioned on the first side (e.g., distal side) of the target tumor 80, which allows the ablation electrode 234 to be positioned between the two impedance monitoring electrodes 237 and 537, for example, within the tumor 80. In this configuration, the current passing between electrodes 237 and 537 to monitor impedance and phase may pass directly through the tumor 80, as indicated by the dashed line 540.

[0280] [Implementation of the System Control Algorithm]

[0281] The system may employ various means for perfusing the ablation element. Peristaltic pumps, injection pumps, and inflators / deflaters may be used. Without limiting the scope of the present invention, in the case of a peristaltic pump, the perfusation flow rate may be indirectly controlled by controlling the rotational speed of the pump head. The pump is adjusted to produce a coefficient for converting its rotational speed to the perfusation flow rate. For example, a rotational speed in the range of 20 to 100 rpm may be used to produce a flow rate in the range of 2 to 10 ml / min. In this embodiment, the conversion coefficient for converting rotational speed to perfusation flow rate would be 0.1 mL / min / rpm.

[0282] Instead of flow rate, the controller may control the bolus dose of the hypertonic solution (or any of the other aqueous solutions mentioned above). For example, a 10 ml bolus dose corresponds to being activated for 5 minutes at a perfusion rate of 2 ml / min. Boluses up to 60 ml may be used.

[0283] Next is a description of an embodiment of a pump control algorithm, which may be part of software 292 stored in an ablation console 291 for controlling a pump 294 to deliver conductive fluid from a conductive fluid supply unit 293 to catheters 220, 255, 270 (Figure 11). This algorithm may function to operate the pump during the preparation and ablation phases to maintain the temperature within a target range. The temperature may be measured by a temperature sensor in the ablation electrode 234 and may be representative of the tissue temperature. The temperature may also represent the electrode temperature or the temperature of the conductive fluid in contact with the ablation electrode. Unlike proportional-integral-derivative (PID) type controls known in the art, this invention controls the flow rate of the pump with three objectives: to maintain the temperature within a range known to be therapeutically effective, to avoid sudden increases in impedance and temperature, and to optimize the amount of hypertonic fluid injected into the patient's lungs. For example, a PID controller would typically decide to control the flow rate to be substantially constant or within a narrow range once the temperature reaches a therapeutic level. Instead, the controller according to the present invention controls the flow rate between low and high flow rates, even if the temperature has already reached the target range. Therefore, the controller according to this disclosure intentionally introduces flow rate variability into the system with the aim of minimizing the total amount of hypertonic saline injected within an effective operating range. Those skilled in the art may decide to use a gradient flow rate rather than a fixed low-high flow rate. The flow rate may be increased gradually rather than increasing it from a low value to a high value, for example. Similarly, various predictive algorithms may be employed to control the flow rate. If the system detects a rapid rise in temperature, the flow rate will be adjusted more significantly in anticipation of the temperature rise to avoid overheating. Similarly, if the system detects a rapid drop in temperature, the flow rate will be reduced more significantly to avoid large temperature fluctuations. Modified PID algorithms may also be used with nonlinear flow rate adjustments that respond to error values ​​(i.e., the difference between the actual flow rate and the set flow rate).A similar control concept may be used when the control parameter is a bolus dose of hypertonic saline.

[0284] The pump control algorithm is executed whenever it receives new impedance or temperature data input from the ablation console. Impedance inputs may arrive at 40-millisecond intervals. Temperature data inputs may arrive at 10-millisecond intervals. The algorithm is illustrated in the flowchart shown in Figure 16A, with further details illustrated in Figures 16B, 16C, and 16D. The output of the pump control algorithm is the commanded flow rate. Additionally, the algorithm may make decisions related to managing overheating or high-impedance conditions. In such situations, power may be temporarily adjusted downward to return temperature and impedance to their normal ranges. Alternatively, if the overheating or high-impedance condition persists for a predetermined duration, the algorithm may decide to terminate energy transfer. If this differs from the previous commanded flow rate, a new flow rate request is sent to the pump. It should be noted that the algorithm in the embodiments of this disclosure does not immediately stop RF transfer if an overtemperature or overimpedance condition occurs. Rather, the algorithm attempts to correct such conditions by optimally adjusting the flow rate of hypertonic saline.

[0285] In box 610, the algorithm calculates whether the High Flow Rate and Overheat Flow Rate settings need to be adjusted.

[0286] After calculating the setpoint adjustment, the algorithm executes the main pump control state machine (box 611). The state machine selects one of three flow rates to be delivered to the pump: Low Flow Rate, High Flow Rate, and Overheat / Over-impedance Flow Rate. Additionally, pre- and post-cooling flow rates may be used for their respective purposes: to improve electrical contact between the airway and electrodes and to cool the airway after ablation. However, the output of the state machine is a numerical value in mL / min, not an enumeration. When the state machine selects a flow rate, it outputs the current setpoint corresponding to that flow rate. For example, if the state machine selects the overheat / over-impedance flow rate and the current setpoint for the overheat / over-impedance flow rate is 6 mL / min, the state machine outputs 6 mL / min. For simplicity, the description herein uses the same flow rates for the overheat and over-impedance states. Different values ​​for the overheat and over-impedance flow rates may be used without departing from the spirit of this disclosure. These would be referred to as state machine (SM) commanded flow rates.

[0287] If the temperature or impedance exceeds the respective thresholds for overheating or overimpedance, the controller may instruct the pump to increase the flow rate to the overheating or overimpedance flow rate value. By doing so, the system attempts to avoid tissue overheating or boiling of the hypertonic saline. Once the flow rate has increased to these higher levels, the controller may decide to maintain the flow rate at such levels for a certain period, even if the overheating or overimpedance condition has been resolved. By doing so, the controller attempts to reduce the likelihood of a recurrence of the overheating or overimpedance condition.

[0288] For the purposes of this embodiment, if the setpoint adjustment calculation unit determines that the flow rate setpoint needs to be changed, the commanded flow rate is adjusted to match the new setpoint (box 613). For example, suppose at the start of the algorithm, the high flow rate = 2 mL / min and the superheating flow rate = 6 mL / min. Then, suppose the setpoint adjustment calculation unit calculates pending setpoints, namely high flow rate = 4 mL / min and superheating flow rate = 8 mL / min. If the state machine (SM) commanded flow rate is 2 mL / min (the current value for high flow rate), the commanded flow rate is adjusted here to 4 mL / min (the new value for high flow rate). On the other hand, if the SM commanded flow rate is equal to the low flow rate, the low flow rate setpoint is not dynamically changed and therefore will not be modified here. The output of this section will be called the commanded flow rate. This is what is sent to control the pump. Generally, when the temperature exceeds the T_High threshold, the flow rate is controlled to high flow rate by state machine elements 611, 612, 613 and 614. Conversely, when the temperature drops below the T_Low threshold, the flow rate is controlled to a low flow rate by the same elements shown in Figure 16A. The high and low flow rate levels can be adjusted automatically by the controller / state machine or manually by the user. For example, if the controller determines after a certain period (which can be programmed manually or automatically) that the high flow rate level is not effective in lowering the temperature to a level below T_Low, the controller can automatically increase the high flow rate to a higher percentage, thereby making the cooling more effective. Conversely, when the cooling is very effective, the controller may decide to reduce the high flow rate to a lower level, minimizing the amount of hypertonic saline injected. These details are illustrated in Figure 16B. The same concept also applies to controlling the low flow rate and the overheating / overimpedance flow rate. The overheating and overimpedance state machines are shown in Figures 16D and 16E, respectively.

[0289] Then, any pending setting changes (if any) are broadcast (i.e., widely transmitted) to the rest of the system (box 614). The new settings will be immediately reflected in the high flow and overheated flow spin boxes in the UI.

[0290] A more detailed diagram of the steps for calculating pending flow rate setpoint adjustments 610 and 611 (Figure 16A) is shown in Figure 16B. The setpoint adjustment algorithm is divided into three parts depending on whether the measured temperature is less than T_Low 620, between T_Low and T_High 621, or greater than or equal to T_High 622. For example, if the temperature is below T_Low (623) because the system has already reached a superheated state, but the superheating flow rate was effective in bringing the temperature back below T_Low, the state machine decides to increase the flow rate setpoint (624). The rationale is that if the high flow rate had been greater, it would have been possible to avoid entering the superheated temperature range. If the temperature is above T_High, but the flow high time is greater than or equal to the maximum flow high duration (625), the state machine determines that the current high flow rate is not effective in bringing the temperature back below T_Low (625). As a result, the flow rate setpoint is increased (626). If the temperature is below T_High but does not fall below T_Low within a sufficiently long time (i.e., remains between T_Low and T_High for a very long time), the state machine determines that the current high flow rate was not effective (627). As a result, the flow rate setpoint is increased (628). Otherwise, the flow rate setpoint is not increased (629). As an example, the following setpoints may be used: T_Low = 85°C, T_High = 95°C, low flow rate (Flow_Low) = 0 mL / min, high flow rate (Flow_High) = 4 mL / min, high flow rate time (Flow_high_time) = 5 seconds. Other values, for example, T_Low may be in the range of 60°C to 95°C, T_High may be in the range of 75°C to 105°C, the low flow rate may be in the range of 0 to 5 mL / min, the high flow rate may be in the range of 2 to 16 mL / min, and the high flow rate time may be in the range of 1 to 30 seconds, but these may be used with equivalent effectiveness. Although a similar concept, conversely, when the current flow rate is very effective, it may be applied to reduce the flow rate. By doing so, the total amount of hypertonic saline injected is optimized. Other thresholds may be adopted by those skilled in the art without departing from the spirit of the present invention.

[0291] The overall state machine of the system is illustrated in more detail in Figure 16C. The four states of the state machine include idle 630, pre-cooling 631, normal cooling 632, and post-cooling 633. Solid arrows represent transitions between states. The conditions that trigger a transition are shown as sentences written directly on the arrows. For example, the transition "Normal Cooling Time Exceeded" 634 indicates that the state machine transitions to the post-cooling state 633 when the duration of the normal cooling state exceeds the normal cooling time setpoint. Boxes with small circles attached to transitions represent actions performed when the state machine goes through a transition. For example, the transition action box 635 with the text "Turn off RF power" indicates that the RF power is turned off when the state machine transitions from normal cooling 632 to post-cooling 633.

[0292] The normal cooling state 632 is the most complex state in this state machine, and its details are shown in Figures 16A and 16B. In this state, the system transmits RF energy to the catheter. Each time the normal cooling state is performed, the overheating 637 (Figure 16D) and overimpedance 638 (Figure 16E) states are also checked. If the temperature is too high during the simple temperature control sub-operation 636, the flow rate is increased; if the temperature is too low, the flow rate is decreased. However, if the sub-state machine 636 determines that the temperature or impedance has reached an overheating or overimpedance state, it requests sub-state machines 637 or 638, respectively. When the temperature state machine sub-operation 637 is requested, the state machine is responsible for performing more complex calculations and requesting an overheating flow rate if the temperature exceeds T_Overheat. For example, T_Overheat may be set to 105°C, and the overheating flow rate (Overheat_Flow) may be equal to 12 mL / min, however other values ​​are also possible. For example, T_Overheat may be in the range of 85–115°C, and the overheating flow rate may be 4–14 mL / min. This condition machine is performed after the simple temperature control 636 and therefore takes precedence over the result. Treatment may also be interrupted if the temperature exceeds T_overheat for an extended period. Further details of this temperature condition machine are shown in Figure 16D. Similarly, if 636 detects an overimpedance condition and requests an impedance condition machine sub-operation 638, the condition machine modifies the pump flow rate based on the measured monopolar impedance. Its purpose is to increase the flow rate and maintain the impedance below Z_high. For example, Z_high may be set to 600Ω and the overimpedance flow rate may be 12 mL / min, although other values ​​may be equally used. For example, Z_high may be substantially in the range of 300–1500Ω. The overimpedance flow rate parameter may be substantially in the range of 6–20 mL / min. Since this instruction is executed after the temperature state machine 637, it may take precedence over the results of the temperature state machine in order to increase the flow rate. However, it will not take precedence for lower flow rates.Further details of this impedance state machine are shown in Figure 16E.

[0293] Figure 17A shows the results of the state diagrams presented in Figures 16A-16E, where temperature 505 and flow rate 506 are plotted against time. RF ablation energy is started at a constant power of 60W for 2 minutes, starting at 5 seconds. Prior to this, during the pre-cooling phase from 0 to 5 seconds, the pump is operated at a flow rate of 5 ml / min, which prepares the system and delivers a small amount of hypertonic saline into the airway through the ablation electrodes. At 5 seconds, the normal cooling state is entered, RF is transmitted (i.e., the power is increased from 0 to 60W), the flow rate is 0, and the normal cooling timer is started. The temperature rises rapidly and reaches the upper threshold (T_High) of 95°C. The controller sets the flow rate to 4 ml / min. Initially, 4 ml / min was effective as the temperature dropped below T_Low (85°C). As a result, in this particular example, the flow rate was returned to a low flow rate of 0 ml / min. The temperature then began to rise again, exceeding T_High. As a result, the flow rate was set again to a high flow rate of 4 ml / min. However, considering that this approximately 4 ml / min was not effective in lowering the temperature to below T_Low (85°C) after a certain period of high flow rate time (set to 5 seconds in this embodiment), i.e., longer than the maximum duration, the controller increased the high flow rate to 6 ml / min and reset the high flow rate time. However, again, after a high flow rate time of 5 seconds, the high flow rate (set to 6 ml / min) was not effective in lowering the temperature to below T_Low, so the controller increased the high flow rate to 8 ml / min. This new high flow rate of 8 ml / min was effective in lowering the temperature. In this way, after the temperature had fallen below T_Low (85°C), the controller set the flow rate to a low flow rate (0 ml / min in this embodiment). A more detailed examination of the above reveals that the flow rate of the conductive fluid causes a temperature drop below the lower threshold (T_Low) of 85°C, which occurs around 8 seconds. Referring to Figure 16B, in this state, the temperature is below T_Low (620°C), and the flow rate is 0. When the temperature rises but remains below T_High, the flow rate remains 0 mL / min.Approximately 10 seconds, the temperature reaches the upper threshold (T_High), which causes the flow rate to become a superheating flow rate of 4 mL / min for a duration of 5 seconds (the minimum duration of high flow). After 5 seconds, the temperature is neither below T_Low nor above T_High (621), and the current high flow rate of 4 mL / min is not effective in bringing the temperature below T_Low (627). Therefore, the flow rate is increased to 6 mL / min (628), and the high flow time is reset to 0 seconds. This new flow rate of 6 mL / min is applied for 5 seconds, until the temperature is again neither below T_Low nor above T_High (627), and the flow rate is increased again to 8 mL / min. Before reaching the 5-second high flow time, the temperature reaches the lower threshold (T_Low), and the flow rate drops to 0 mL / min, remaining at this flow rate until the temperature rises and reaches the upper threshold, which is seen at approximately 28 seconds. A current flow rate of 8 mL / min is triggered and run for 5 seconds. Again, the temperature does not drop below T_Low at 8 mL / min, so the flow rate is increased to 10 mL / min. Before the 5 seconds are up, the temperature reaches T_Low and the flow rate decreases to 0 mL / min. At approximately 43 seconds, the temperature reaches T_High, and the current flow rate of 10 mL / min is triggered for another 5 seconds. Since 10 mL / min was not effective in bringing the temperature to T_Low, the flow rate is increased to 12 mL / min at this point. At approximately 51 seconds, the temperature reaches T_Low and the flow rate becomes 0. With a flow rate of 0 mL / min, the temperature rises again, reaching T_High at approximately 57 seconds, triggering a current flow rate of 12 mL / min. After 5 seconds, the flow rate is determined to be effective and remains at 12 mL / min until the temperature reaches T_Low at approximately 70 seconds. When the flow rate drops to 0 mL / min and the temperature reaches T_High in approximately 76 seconds, a current flow rate of 12 mL / min is triggered. This flow rate effectively lowers the temperature and maintains it between T_High and T_Low until the temperature reaches T_Low and the flow rate is set to 0 in approximately 115 seconds. In this embodiment, since 12 mL / min was programmed as the maximum allowable high flow rate level, the flow rate did not increase further even though the high flow time of 5 seconds was exceeded. Other maximum levels may also be used by those skilled in the art.At approximately 122 seconds, the temperature reaches T_High again, and the flow rate is set to 12 mL / min. At 125 seconds, the normal cooling timer ends, the RF power is turned off, and the flow rate is set to 0 as the post-cooling phase begins. Figure 17B shows the system behavior when the power is gradually increased. Rather than applying power steps (e.g., 0-60W), in Figure 17B, the power was gradually increased to a constant value from 40W to approximately 75W. In such a control plan, the power was maintained at 40W for the first 30 seconds, and then increased for the next 30 seconds, for example, to 50W, until the target maximum power level was reached. The advantage of such a power control algorithm lies in the reduction of the possibility of tissue rupture or tissue cavity. Both tissue rupture and cavity indicate potential safety concerns, as they can cause pneumothorax.

[0294] [Second Embodiment of System Control Algorithm]

[0295] The second system control algorithm is described below, but the controller is used to adjust the flow rate of conductive fluid, the RF power control algorithm adjusts the RF electrodes, and the total amount of conductive fluid delivered or conditions representing the total amount of conductive fluid delivered are monitored, thereby avoiding, for example, the delivery of excess conductive fluid. An example plot of an ablation procedure using this control algorithm is shown in Figure 20. The second system control algorithm may also be part of the software 292 stored in the ablation console 291 to control the pump 294 to deliver conductive fluid from the conductive fluid supply unit 293 to the catheters 220, 255, 270, and to transmit ablation energy from the ablation console 291 to the ablation catheters 220, 255, 270 (Figure 11), in particular to the ablation electrodes 234, 250, 434, 534 on the ablation catheters. This algorithm may operate a pump during the preparation and ablation phases to deliver conductive fluid within a desired total volume, for example, below a desired maximum volume, or within a total volume that brings about a set of conditions, in order to maintain the temperature within the target range. The above temperature may be measured by temperature sensors in the ablation electrodes 234, 250, 434, 534, and may be representative of the tissue temperature. The above temperature may represent the electrode temperature or the temperature of the conductive fluid in contact with the ablation electrode.

[0296] While the delivery of a conductive fluid (e.g., hypertonic saline) during RF energy transfer is advantageous for achieving ablation of lung tumors, excessive delivery of conductive fluid to the target lung site may have adverse effects. For example, excessive fluid may produce ablation larger than intended, or it may fill the target lung site and leak out, potentially causing inflammation or damage to non-target tissue. Therefore, the objective of the second system control algorithm is to deliver sufficient conductive fluid (e.g., hypertonic saline) to ablate the target lung tumor while avoiding the delivery of excessive conductive fluid, which could increase safety risks.

[0297] The procedure may include a lung volume reduction phase, a preparation phase in which conductive fluid is delivered to fill the fluid delivery tube and moisten the ablation electrodes before the transfer of RF ablation energy, a perfusion ablation phase in which conductive fluid is delivered and ablation RF energy is transferred, and a non-perfusion ablation phase in which conductive fluid is present in the target site of the lung but no more is added and ablation RF energy is transferred. The lung volume reduction phase in which suction force is applied to the occluded target site of the lung, including the target tumor, may be described in more detail herein and may include various occluding elements, impedance sensors, vacuum pumps, or control algorithms. Throughout the entire procedure, including all phases, the total cumulative volume of conductive fluid may be calculated (e.g., based on flow rate or pump speed and time) and may be displayed on the console user interface as needed. When the patient starts the procedure, the user may reset the total calculated volume. The maximum total volume of conductive fluid may be predetermined, for example, in the range of 10 mL to 20 mL. Alternatively, the maximum total volume of conductive fluid may be a user-defined parameter set before the start of the procedure, and may be adjusted as needed during the procedure, for example, at the physician's discretion, based on the volume of the target site, visual indicators such as those seen through a bronchoscope, or the patient's response. Alternatively, the maximum total volume of conductive fluid may be calculated as a function of parameters such as the desired ablation volume, the volume of the target lung site, proximity to the pleura or other tissue, proximity to the center of the tumor, and the patient's physique, and may be adjustable by the user during the procedure as needed.

[0298] Following the lung volume reduction and preparation phases, the user may activate the start button to initiate the perfusion ablation phase. In this phase, ablation RF power is transmitted and conductive fluid is perfused through the ablation electrodes. Inputs to the control algorithm during this phase may include target ablation electrode temperature, measured ablation electrode temperature, monopolar impedance, monopolar phase, bipolar phase, and bipolar impedance. The algorithm may receive time or duration data from the timing circuit. The algorithm may output a set RF ablation power amplitude profile, perfusion pump speed or on / off setpoint, and total cumulative amount of conductive fluid (e.g., HTS). The RF power may be set to a constant amplitude in the range of, for example, 50W to 80W (e.g., 55W to 75W, 55W to 65W, 60W), and this amplitude may be maintained for the remainder of the perfusion ablation phase. If necessary, the RF power may be gradually increased in response to a sudden increase in impedance caused by a specific event, such as patient movement or drying of tissue adjacent to the electrode, and may be reduced or interrupted until the impedance stabilizes. If necessary, the RF power may initially increase from 0W to a constant amplitude over a period of, for example, up to 30 seconds (e.g., up to 25 seconds, up to 20 seconds, up to 10 seconds). During this phase, the conductive fluid may be delivered in a bolus or flow rate determined by a control algorithm to adjust the measured electrode temperature to match a target temperature. For example, the control algorithm may use a PID controller or a modified PID controller to control the flow rate of the conductive fluid to perfuse the target site and maintain the measured temperature at or near the target temperature. The target temperature may be in the range of 80°C to 100°C (e.g., in the range of 85°C to 95°C, approximately 90°C).If necessary, when the measured temperature is within a range close to the set temperature (e.g., within 4°C or 5% of the set temperature), the perfusion may be set to 0 mL / min or a very low flow rate (e.g., less than 1 mL / min or less than 0.5 mL / min), which may further contribute to minimizing the total amount of fluid delivered. For example, if the measured temperature is above 95°C and the set temperature is 90°C, the perfusion may be turned on to lower the measured temperature, and when the measured temperature reaches 94°C, the perfusion may be turned off. The control algorithm may continue the perfusion ablation phase until the total cumulative amount of fluid delivered reaches or approaches a predetermined maximum amount, at which point it transitions to the non-perfusion ablation phase. If necessary, when the total cumulative amount approaches the maximum amount, for example, within 2 mL of the maximum amount, the RF power amplitude may be reduced, for example, by an amount in the range of 5W to 20W.

[0299] During the non-perfusion ablation phase, the conductive fluid is present in the target lung site from the preceding perfusion ablation phase, perfusion is stopped to avoid delivering excess fluid, and the control algorithm gradually increases the RF power, for example, using a PID controller or a modified PID controller, to bring the measured temperature to a set temperature. The set temperature may remain the same as in the preceding perfusion ablation phase (e.g., 90°C) or may be changed. If necessary, the RF power may be changed in small increments (e.g., increments of 5W).

[0300] To determine whether the algorithm is in the perfusion ablation or non-perfusion ablation phase, the algorithm may use other inputs or conditions instead of comparing the measured cumulative fluid volume with a predetermined maximum volume. For example, conditions indicating that perfusion fluid is leaking or may leak from the occluded lung space may cause the algorithm to transition to the non-perfusion phase. These triggers may also identify device malfunctions, such as a ruptured occlusion balloon. Fluid leakage conditions may be determined using sensors on the ablation catheter. For example, a temperature sensor proximal to the occlusion element may show an increase if hot fluid leaks and comes into contact with the sensor. If necessary, an acceptable temperature increase proximal to the occlusion element, such as an increase due to heat conduction along the catheter shaft, may not cause a change, but a sudden temperature change (e.g., an increase of at least 5°C per second) may cause a change to non-perfusion ablation or interrupt all perfusion and RF transmission until the user instructs the algorithm to continue. Impedance measured from a sensor proximal to the occluding element may indicate leakage if it decreases. Bipolar impedance distal to the balloon may be used to assess fluid volume. Pressure measured within the occluded space, compared to ambient pressure or pressure proximal to the occluding element, may increase as fluid is delivered, and a maximum set pressure difference may cause the algorithm to stop or interrupt perfusion and transition to the non-perfusion ablation phase. For example, if the user notices a patient coughing or sees fluid leakage via bronchoscopy, the user may input a signal through the user interface to manually interrupt the perfusion ablation phase and transition to the non-perfusion ablation phase.

[0301] If necessary, the algorithm may transition to the non-perfusion ablation stage based on the detected condition, but if the predetermined maximum total amount has not been reached, and the detected condition is alleviated, the algorithm may transition back to the perfusion ablation stage.

[0302] If necessary, when the total fluid volume reaches or approaches the maximum total volume, the fluid may be allowed to leak out of the occluded lung space through the lumen in the ablation catheter, and optionally through the guidewire lumen, by, for example, manually or automatically opening a valve. The amount of saline that leaks out may be measured (for example, by weighing it or measuring it with a flow meter) and subtracted from the cumulative total volume, and the perfusion ablation stage may be continued until the maximum fluid volume is reached.

[0303] The system may employ various means for perfusing the ablation element. Peristaltic pumps, injection pumps, and inflators / deflaters may be used. Without limiting the scope of the present invention, in the case of a peristaltic pump, the perfusation flow rate may be indirectly controlled by controlling the rotational speed of the pump head. The pump is adjusted to produce a coefficient for converting its rotational speed to the perfusation flow rate. For example, a rotational speed in the range of 20 to 100 rpm may be used to produce a flow rate in the range of 2 to 10 ml / min. In this embodiment, the conversion coefficient for converting rotational speed to perfusation flow rate would be 0.1 mL / min / rpm.

[0304] Instead of flow rate, the controller may control the bolus dose of the hypertonic solution (or any of the other aqueous solutions mentioned above). For example, a 10 ml bolus dose corresponds to being activated for 5 minutes at a perfusion rate of 2 ml / min. Boluses up to 60 ml may be used.

[0305] If necessary, during the perfusion ablation stage, the conductive fluid may be selected by a control algorithm from a plurality of sources having various properties, such as hypertonic saline and physiological saline for edema relief as described herein.

[0306] Those skilled in the art may decide to use a gradient flow rate rather than a fixed low-to-high flow rate. The flow rate may be increased gradually rather than, for example, from a low value to a high value. Similarly, various predictive algorithms may be employed to control the flow rate. If the system detects a rapid rise in temperature, the flow rate will be adjusted more significantly in anticipation of the temperature rise, thus avoiding overheating. Similarly, if the system detects a rapid drop in temperature, the flow rate will be reduced less significantly, thus avoiding large temperature fluctuations. Modified PID algorithms can also be used with nonlinear flow rate adjustments that respond to error values ​​(i.e., the difference between the actual flow rate and the set flow rate). A similar control concept may be used when the control parameter is a bolus dose of hypertonic saline.

[0307] The pump control algorithm is executed whenever it receives new impedance or temperature data input from the ablation console. Impedance inputs may arrive at 40-millisecond intervals. Temperature data inputs may arrive at 10-millisecond intervals. The output of the pump control algorithm is the commanded flow rate. Additionally, the algorithm may make decisions related to managing overheating or high impedance conditions. In such situations, power may be temporarily reduced to return temperature and impedance to their normal ranges. Alternatively, if the overheating or high impedance condition persists for a predetermined duration, the algorithm may decide to terminate energy transfer. If the flow rate differs from the previous commanded flow rate, a new flow rate request is sent to the pump.

[0308] The systems, catheters, and apparatus described above and / or claimed may utilize at least one controller. This controller may comprise a digital processing unit (CPU) having memory (or multiple memories), an analog circuit, or a combination of one or more digital processing units having one or more analog processing circuits. In this specification and in the claims, it is indicated that the controller is “configured” or “programmed” to perform a particular step. This may be actually realized by any means that enables the controller to be configured or programmed. For example, if the controller comprises one or more CPUs, one or more programs are stored in appropriate memory. A program or a set of programs, which, when executed by the controller, contain instructions causing the controller to perform a step, is described and / or claimed in relation to the controller. Alternatively, if the controller is analog, the controller's circuitry is designed to include electrical circuits configured to process electrical signals during use, such as subsequently performing the controller steps disclosed and / or claimed herein.

[0309] While at least one exemplary embodiment of the present invention is disclosed herein, modifications, substitutions, and alternatives will be obvious to those skilled in the art and should be understood to be made without departing from the scope of this disclosure. This disclosure is intended to cover all adaptations or modifications of the exemplary embodiment. In addition, in this disclosure, the terms “comprise” or “comprising” do not exclude other elements or steps, the terms “a” or “one” do not exclude multiple elements or steps, and the term “or” means either or both. Furthermore, the features or steps described may be used in combination with other features or steps and in any order, unless the disclosure or context suggests otherwise. This disclosure is incorporated herein by reference to the complete disclosure of any patent or application claiming interest or priority.

Claims

1. A system for treating targeted sites in lung tissue, A catheter configured to advance through the bronchi into the airway of the lung in order to position its distal end at or near a target site in the lung tissue, A flow regulator configured to be interposed between a conductive fluid source and a conductive fluid outlet located at the distal end of the catheter, configured to control the flow rate or bolus dose of the conductive fluid delivered from the conductive fluid source to the target site through the conductive fluid outlet, wherein the conductive fluid is sodium chloride at a concentration of 20% to 30%, and the flow regulator An ablation electrode attached to the distal end of the catheter, It is a controller, Control the transfer of power from the ablation energy source to the ablation electrode. In the first operating mode, the flow regulator is controlled to adjust the flow or bolus delivery of the conductive fluid to the conductive fluid outlet, thereby maintaining the temperature at the target site or the distal end of the catheter within a first temperature range. Determine the amount of conductive fluid delivered through the conductive fluid outlet, To prevent the amount of conductive fluid from reaching a threshold amount, the flow of conductive fluid to the conductive fluid outlet or the bolus administration of the conductive fluid is stopped or reduced. In the second operating mode, the temperature at the target site or distal portion of the catheter is maintained within a second temperature range by adjusting the power transfer to the ablation electrode while stopping or reducing the flow of the conductive fluid to the conductive fluid outlet or bolus delivery. A controller configured as follows, Equipped with, The first temperature range and the second temperature range overlap, A system in which the first operating mode and the second operating mode are performed alternately.

2. The system according to claim 1, wherein the first and / or second temperature range is a temperature range of 80°C to 100°C.

3. The system according to claim 1, wherein the first and / or second temperature range is a temperature range of 85°C to 95°C.

4. The system according to claim 1, wherein the first and / or second temperature range is a temperature range of 86°C to 94°C.

5. The system according to claim 1, wherein the first and / or second temperature range is 90°C.

6. The system according to claim 1, wherein the first and second temperature ranges are the same.

7. A system according to any one of claims 1 to 6, wherein the step of controlling the flow regulator includes stopping or minimizing the flow of the conductive fluid to the conductive fluid outlet while the temperature of the target portion is a predetermined temperature within the first temperature range.

8. A system according to any one of claims 1 to 7, wherein the threshold amount is in the range of 10 mL to 20 mL.

9. A system according to any one of claims 1 to 7, wherein the threshold amount is one of 20 ml, 15 ml, and 10 ml.

10. A system according to any one of claims 1 to 9, wherein the controller sets the power to be transmitted to the ablation electrode such that the amount of conductive fluid is transmitted to the ablation electrode at a constant power level while power is applied to the ablation electrode until the amount of conductive fluid reaches the threshold amount.

11. A system according to any one of claims 1 to 10, wherein the power transmitted to the ablation electrode is maintained within the range of 50W to 80W.

12. A system according to any one of claims 1 to 10, wherein the power transmitted to the ablation electrode is maintained within the range of 55W to 75W.

13. A system according to any one of claims 1 to 10, wherein the power transmitted to the ablation electrode is maintained within the range of 55W to 65W.

14. A system according to any one of claims 1 to 10, wherein the power transmitted to the ablation electrode is maintained within the range of 57W to 63W.

15. A system according to any one of claims 11 to 14, wherein the power transmitted to the ablation electrode is reduced by 5W to 20W after the flow of the conductive fluid is stopped.

16. A system according to any one of claims 1 to 15, wherein, after the amount of conductive fluid reaches the threshold amount, the controller reduces the power transmitted to the ablation electrode to a level below the power level transmitted to the ablation electrode while the conductive fluid is being delivered to the conductive fluid outlet.

17. A system according to any one of claims 1 to 16, wherein the controller is further configured to control the flow regulator to adjust the salinity of the conductive fluid delivered to the conductive fluid outlet.

18. A system according to any one of claims 1 to 17, wherein the controller is a proportional-integral-derivative (PID) controller.

19. A system according to any one of claims 1 to 18, wherein the controller is The system is further configured to receive a value detected by a sensor that detects the value of a control parameter representing at least one of the physical properties of a substance present in or near a target site of the lung tissue, namely temperature (T), pressure (P), electrical impedance (Z), and conductivity (C). The aforementioned controller, The power transmitted to the ablation electrode is controlled based on at least one of the control parameters, and / or The flow regulator is controlled to adjust the flow of the conductive fluid delivered to the conductive fluid outlet based on at least one of the control parameters. A system further configured in this way.

20. A system according to any one of claims 1 to 19, The system further comprises a first closure plug attached to a flexible shaft proximal to the ablation electrode and proximal to a fluid outlet, wherein the first closure plug is configured to expand to occlude the airway.

21. The system according to claim 20, wherein the outer diameter of the assembly of the flexible shaft and the ablation electrode is 2.0 mm or less.

22. A system according to any one of claims 1 to 21, wherein the controller is The sensor receives a value detected by a sensor positioned outside the target site within the lung tissue, and the sensor detects a value of a control parameter that represents a physical characteristic of the lung tissue outside the target site, which is at least one of the following: temperature (T), pressure (P), electrical impedance (Z), and conductivity (C). Depending on the value detected and received by the sensor, the delivery of the conductive fluid flow to the conductive fluid outlet is reduced or stopped. A system further configured in this way.

23. The system according to claim 22, wherein the delivery of the flow of the conductive fluid to the conductive fluid outlet is reduced or stopped in response to the controller's determination that the received value indicates the introduction of the conductive fluid into lung tissue outside the target site.

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