Devices and methods for treating lung tumors

Abstract

The present disclosure relates to methods, devices, assemblies and systems for transbronchial ablation of lung tumors. Aspects of the disclosure include: A radio frequency (RF) ablation catheter configured to heat a passageway filled with liquid metal, the ablation catheter comprising a flexible shaft having a distal end and a proximal end, the flexible shaft having a fluid channel configured to drip the liquid metal into the passageway. The ablation catheter further comprises an inflatable balloon mounted on the flexible shaft, a portion of the flexible shaft distal to the balloon defined as a distal segment of the flexible shaft, the balloon configured to occlude the passageway. The ablation catheter comprises an RF conductor located in the distal segment and configured to couple RF energy to the liquid metal to heat the passageway.

Description

Technical Field

[0001] The present disclosure generally relates to devices and methods for ablating lung tumors, and more particularly, relates to ablation treatment of lung tumors by using liquid metal as an electrode. Background Art

[0002] To date, thermal ablation has become an increasingly attractive option for the treatment of unresectable tumors in the lung. Radiofrequency (RF) energy has been considered to be the most useful for lung ablation. However, there are major technical deficiencies in the delivery of RF energy to the lung. The use of multi-prong electrodes that increase total electrode surface area, and infusion of ionic fluids, have been shown to reduce impedance to RF current flow in the lung. While these techniques are effective, they are not without drawbacks. Fluid infusion is unpredictable and has been associated with an increased risk of complications. Multitined electrodes increase invasiveness, can be difficult to use in solid tumors located within normal lung tissue, and have been associated with abnormal ablation zones and an increased incidence of pneumothorax.

[0003] In addition, various radiofrequency ablation (RFA) procedures have been used for the treatment of peripheral lung tumors. However, there remains a need for improvement due to insufficient ablation coverage and the difficulty of endoscopically navigating the ablation electrode to the target tumor in peripheral pulmonary lesions (PPL). For ablating tumors closer to the periphery of the lung, it is desirable that the ablation electrode is flexible, relatively soft, has a small diameter, and is preferably adapted to PPL smaller than 2 mm.

[0004] While radiofrequency (RF) ablation is a treatment for lung tumors, the requirement to precisely deliver a rigid metal electrode to the center of the target site in peripheral lung lesions often results in a risk of damage to surrounding areas or suboptimal ablation. [Overview of the project]

[0005] To address the requirement of precisely delivering a rigid metal electrode to the center of the target site, RF ablation catheter devices utilize medical-grade liquid metal devices instead of solid electrodes. The liquid metal device acts as an electrode, through which RF ablation energy can be applied to the lung tumor. Upon injection into the target site, the liquid metal device adapts to the anatomical structure of the target site. This adaptable shape of the liquid metal device results in a lower risk of damage to surrounding areas. The liquid metal device is easily removed by suction without damaging surrounding areas. Therefore, the liquid metal device acts as an independent, flexible electrode within the target site, generating a larger ablation area.

[0006] An RF ablation catheter device configured to ablate a tumor adjacent to a target site using a liquid metal device comprises a flexible shaft configured to advance into the target site within the bronchi. The catheter device further comprises an inflatable balloon attached to the shaft, the portion of the flexible shaft distal to the inflatable balloon defined as the distal segment. The catheter device further comprises an RF conductor attached to the distal segment, configured to allow an RF current to pass through the liquid metal device so that the liquid metal device can deliver radio frequency (RF) energy to ablate the tumor.

[0007] In one embodiment, a radiofrequency (RF) ablation catheter is configured to heat a passage filled with liquid metal, and the ablation catheter comprises a flexible shaft extending between a distal end and a proximal end. The flexible shaft has a fluid channel for dripping the liquid metal into the passage. The ablation catheter further comprises an inflatable balloon attached to the flexible shaft. The ablation catheter further comprises an RF connector. The portion of the flexible shaft distal to the inflatable balloon is defined as the distal segment of the flexible shaft. The RF connector is located in the distal segment and is configured to connect RF energy to the liquid metal, thereby heating the passage.

[0008] In an RF ablation catheter, the distal segment forms a conduit within the distal segment such that the conduit transports liquid metal through a fluid channel. In one embodiment, the RF connector is recessed within the conduit. In one embodiment, the RF connector is located at the proximal end of the distal segment directly adjacent to the inflatable balloon. In one embodiment, the RF connector is a conductive wire connected to an RF generator. The ablation catheter further comprises a temperature sensor mounted on the distal segment of the shaft and configured to read the temperature of the liquid metal. The temperature sensor is recessed within the conduit. The conduit is made of a non-conductive material. Here, the passage is the bronchial airway of the lung.

[0009] In another embodiment, an ablation catheter assembly is configured to heat a passage, and the assembly contains liquid metal contained in a syringe. The ablation assembly further comprises an RF ablation catheter comprising a flexible shaft having a fluid channel for dripping liquid metal into a passage, and an inflatable balloon attached to the flexible shaft and an RF connector, where the portion of the flexible shaft distal to the inflatable balloon is defined as the distal segment of the flexible shaft, and where the RF connector is located on the distal segment and is configured to connect RF energy to the liquid metal, thereby heating the passage.

[0010] The ablation catheter assembly further comprises a flexible bronchoscope having a working channel configured for the ablation catheter to advance through the working channel. The ablation catheter assembly further comprises an RF generator electrically coupled to an RF connector, where the passage is the bronchial airway of the lung. In the ablation catheter assembly, the liquid metal contains gallium, and the liquid metal is E-GaIn.

[0011] In an ablation catheter assembly, the RF ablation catheter does not use solid electrodes for ablation. In the RF ablation catheter, the distal segment forms a conduit within the distal segment in such a manner that the conduit transports liquid metal from a fluid channel. In some embodiments, the RF connector is positioned within the conduit in a recessed manner. In some embodiments, the conduit is made from a non-conductive material.

[0012] A method for treating a tumor in a patient includes (a) inserting an ablation catheter into a passage, (b) advancing an ablation catheter device into the passage, (c) inflating a balloon to occlude the passage, (d) dripping liquid metal into the passage, and (e) applying an RF current to the liquid metal in the passage.

[0013] In the above method, the passage is the bronchial airway of the lung. The method further comprises dropping liquid metal into at least two branches of the bronchial airway. In the above method, the alveoli of the bronchial airway are not filled with liquid metal.

[0014] The above method further comprises (a) having a flexible bronchoscope equipped with an instrument channel, (b) inserting an ablation catheter through the instrument channel of the bronchoscope, (c) advancing the bronchoscope into the passage, and (d) advancing the ablation catheter out of the instrument channel of the bronchoscope into the passage, the passage being a bronchial airway of the lung.

[0015] The above method further includes aspirating the liquid metal out of the passage by suction through a bronchoscope. The above method further includes visualizing the ablation catheter by fluoroscopy while advancing the ablation catheter into the passage. The above method further includes visualizing the liquid metal by fluoroscopy while dripping the liquid metal into the passage.

[0016] In the above method, the amount of liquid metal dropped is less than 1.0 ml. The liquid metal also contains gallium. In some embodiments, the liquid metal is E-GaIn. In the above method, the liquid metal is dropped only into bronchial airways having a diameter of less than 5 mm. In some embodiments, the liquid metal is dropped only into bronchial airways having a length of less than 10 cm. [Brief explanation of the drawing]

[0017] [Figure 1A] This is a perspective view of an ablation catheter. [Figure 1B] This is a perspective view of an ablation catheter. [Figure 1C] This is a side view of an ablation catheter. [Figure 1D] This is a cross-sectional view of AA in Figure 1E. [Figure 1E] This is a side view of the occlusion balloon of an ablation catheter. [Figure 1F] This is a cross-sectional view of a flexible shaft. [Figure 1G] This is an enlarged cross-sectional view of the distal portion of Figure 1F. [Figure 1H] This is a cross-sectional view taken at CC in Figure 1F. [Figure 1I] This is a cross-sectional view of a flexible shaft. [Figure 1J] This is a cross-sectional view taken at BB in Figure 1I. [Figure 2A] These are cross-sections of different embodiments of the catheter. [Figure 2B]It is a cutaway view of a different embodiment of a catheter. [Figure 2C] It is a cutaway view of a different embodiment of a catheter. [Figure 2D] It is a cutaway view of a different embodiment of a catheter. [Figure 2E] It is a schematic view of a portion of an exemplary catheter. [Figure 2F] It is a view showing different embodiments of a catheter having a guide wire. [Figure 2G] It is a view showing different embodiments of a catheter having a guide wire. [Figure 2H] It is a view showing different embodiments of a catheter having a guide wire. [Figure 2I] It is a view showing different embodiments of a catheter having a guide wire. [Figure 3] It is a view showing an ablation catheter assembly. [Figure 4A] It is a view showing an ablation catheter assembly placed in a lung. [Figure 4B] It is a view showing preferred target sites for lung ablation. [Figure 4C] It is a view showing preferred target sites and sensitivity zones. [Figure 4D] It is a view showing a target airway filled with liquid metal. [Figure 4E] It is a view showing the target airway when liquid metal is removed. [Figure 5A] It is a view showing target ablation sites in a peripheral lesion. [Figure 5B] It is a view showing a preferred ablation zone. [Figure 5C](a) shows the target airway filled with liquid metal. (b) shows the ablation size when the target airway is empty. (c) shows the ablation size when the target airway is filled with NaCl. (d) shows the ablation size when the target airway is filled with AuNP. (e) shows the ablation size when the target airway is filled with EGaIn. [Figure 5D] This is a comparison chart showing the ablation area size. [Figure 6A] This diagram shows the steps of the ablation catheter placed at the target site. [Figure 6B] This diagram shows the steps of the ablation catheter placed at the target site. [Figure 6C] This diagram shows the steps involved in dripping liquid metal into the target airway. [Figure 6D] This diagram shows the steps involved in dripping liquid metal into the target airway. [Figure 6E] This diagram shows the steps to complete the dropping of liquid metal. [Figure 6F] This figure shows the steps of applying an RF current to a liquid metal. [Figure 6G] This diagram shows the situation where the target zone is being ablated. [Figure 6H] This diagram shows the situation where the target zone is being ablated. [Figure 6I] This diagram shows the step of sucking up the liquid metal that has been dropped. [Figure 6J] This diagram shows the step of sucking up the liquid metal that has been dropped. [Figure 7A] This figure shows the operating parameters and flowchart. [Figure 7B] This figure shows the operating parameters and flowchart. [Figure 8] This figure shows the steps illustrated in the procedure. [Modes for carrying out the invention]

[0018] Description of Exemplary Embodiments To aid in understanding the present invention, references are made to accompanying drawings for the purpose of illustrating specific embodiments in which the invention can be carried out. The drawings herein are not necessarily to scale or to actual proportions. For example, the lengths and widths of components may be adjusted to correspond to the page size.

[0019] This disclosure relates to methods, devices, assemblies and systems for transbronchial ablation of lung tumors. Aspects of this disclosure include: a radiofrequency (RF) ablation catheter configured to heat a passage filled with liquid metal. The ablation catheter comprises a flexible shaft having a distal end and a proximal end, the flexible shaft having a fluid channel configured to drip liquid metal into the passage. The ablation catheter further comprises an inflatable balloon mounted on the flexible shaft, the portion of the flexible shaft distal to the balloon being defined as the distal segment of the flexible shaft, and the balloon being configured to obstruct the passage. The ablation catheter comprises an RF conductor located on the distal segment and configured to connect RF energy to the liquid metal, thereby heating the passage.

[0020] target site Throughout this disclosure, the target site or region can be referred to as a bronchial tree located between the segmental bronchi (3rd to 4th generation), subsegmental bronchi (5th to 11th generation), bronchioles (12th to 15th generation), and terminal bronchioles (16th generation). Preferred target sites may further include respiratory bronchioles (17th to 19th generation). Figures 4B to 4C show examples of target sites including, for example, tertiary bronchi, small bronchi, bronchioles, terminal bronchioles, and respiratory bronchioles. In some embodiments applicable to internal organs other than the lungs, the target site may be the hepatobiliary duct or pancreatic duct.

[0021] Target airway Throughout this disclosure, the target airway or passage is referred to as the bronchial airway surrounding or adjacent to the target tumor within the target site. Note that the target airway includes the main bronchial airway and its branches, as shown in Figures 4D and 5A-5B. The main bronchial airway may have a tapered shape with a proximal end. In one embodiment, the target airway may have a diameter of less than 0.5 cm at its proximal end. In some embodiments, the target airway may have a length of less than 6 cm. Since the diameter and length of the target airway are closely related to the ablation size, a preferred target airway may be located in the peripheral airway.

[0022] Once the target airway is determined, the operator can determine one of the occlusion balloon positions (i.e., A, B, or C) positioned in the proximal portion of the target airway, as illustrated within the target site in Figure 4B, to close the selected target site. By dropping liquid metal onto the closed target site, the dropped liquid metal can adapt to the anatomical structure of the main airway and its branches and act as an electrode, through which RF energy can be applied to the tumor.

[0023] Flexible shaft In one embodiment, the ablation catheter 100 includes a flexible shaft 110. Figure 1A shows that the flexible shaft 110 has an occlusion balloon 120 attached to its distal end and a handle portion 130 attached to its proximal end. Figure 1B shows a magnified view of the distal portion of the shaft 110 showing the balloon 120. In one embodiment, the flexible shaft has a length of 50 to 250 cm.

[0024] In one embodiment, the flexible shaft 110 further includes an outer shaft 110a and an inner shaft 110b, each having distal ends 110c and 110d, respectively. The outer shaft 110a has a lumen for insertion of the inner shaft 110b, as shown in Figure 1F. In some embodiments, the outer shaft 110a has an outer diameter of less than 1.65 mm.

[0025] In one embodiment, the inner shaft 110b includes a guidewire lumen 111 having an outer diameter of less than 0.5 mm for the insertion of a guidewire. The inner shaft 110b further comprises a fluid channel 112 having an outer diameter of less than 0.3 mm, as shown in the cross-sectional view (CC) of Figure 1G. The guidewire lumen 111 is configured for the insertion of a guidewire. In some embodiments, the fluid channel 112 is configured for the passage of liquid metal (i.e., dripping or suction).

[0026] In one embodiment, as shown in Figures 1F and 1G, the distal end 110d of the inner shaft 110b may be configured to be at a certain distance from the distal end 110c of the outer shaft 110a. The inner space created by the distance between the outer shaft and the inner shaft is defined as a conduit (cavity) 119a. As shown in Figures 2A and 2D, it is preferable that the conduit 119a creates a channel that is protected or insulated from target airway tissue so that when RF energy is applied, the liquid metal in the conduit 119 or cavity can avoid discontinuities in the liquid metal and direct contact with nearby airway tissue. In some embodiments, the surface of the conduit 119a is made of an electrically insulating material.

[0027] In one embodiment, the distal portion of the inner shaft 110b may be thinned to adhere firmly to the inner lumen of the outer shaft 110a, while the proximal portion thins to form an expansion lumen 113. The expansion lumen 113 is defined as the space between the outer shaft 110a and the inner shaft 110b, as shown in Figures 1F and 1G, for an occluding balloon 120 mounted on the outer shaft 110a for balloon inflation or deflation during treatment. In some embodiments, a separate expansion lumen 113 can be constructed along the flexible shaft, as shown in Figures 2C–2D. The length and size of the conduit 119a may vary depending on the anatomical structure of the target airway. In some embodiments, the length of the conduit 119a may be less than 0.5 cm.

[0028] In some embodiments, the flexible shaft 110 may include an inner shaft 110b and an outer shaft 110a, the outer shaft being positioned to surround the inner shaft 110b so as to cover at least a portion of the inner shaft's length. The flexible shaft 110 extends along the shaft axis between a distal end and a proximal end, and the length of the shaft is defined along the shaft length axis.

[0029] Occlusion balloon In one embodiment, the ablation catheter device 100 further comprises an occlusion balloon 120 mounted on an outer shaft 110a, as shown in Figures 1F and 1H. The balloon 120 is positioned within 4–6 mm of the distal end 110c of the outer shaft 110a. In some embodiments, the ablation catheter 100 may have multiple occlusion balloons (not shown) depending on the anatomical structure of the target airway. In some embodiments, the occlusion balloons may work in conjunction with other balloons equipped on a conventional bronchoscope.

[0030] In one embodiment, the distal portion of the outer shaft 110a of the occluding balloon 120 can be defined as the distal segment 119 of the shaft, as shown in Figure 1B. In some embodiments, the distal segment 119 of the shaft has a length of less than 5.0 mm to avoid direct contact with the target airway tissue.

[0031] In some embodiments, the primary function of the occlusion balloon 120 is to close the entrance to the target airway, which is to be filled with liquid metal 150. In some embodiments, the entrance to the target airway may be, for example, about 4-5 mm in diameter. When the ablation catheter 100 is placed in the target airway, the balloon 120 is configured to close the entrance to the target airway before the liquid metal is released. After the intended ablation is complete, the balloon 120 is deflated, and the ablation catheter 100 is removed from the bronchoscope 170 through the working channel.

[0032] In some embodiments, the flexible shaft 110 may further include an expansion lumen 113 defined by the space between the outer flexible shaft and the inner flexible shaft, which communicates with and is configured to supply or discharge an inflatable / closing balloon 120, as shown in Figures 1F and 1H. The inner shaft 110b may further include a guidewire lumen configured for the insertion of a guidewire. The guidewire may be formed from a conductive material.

[0033] In some embodiments, the inner shaft 110b and the outer shaft 110a may have the same length distal to the inflatable balloon 120 so as to form the distal end of the shaft together, and the RF connector 115 is formed on the distal segment of the outer shaft 110a.

[0034] RF connector In one embodiment, the ablation catheter further includes an RF connector 115. The main function of the connector 115 is to connect RF energy to the liquid metal 150, thereby heating the target airway. Various forms of RF connectors 115 can be used. For example, in one embodiment, a conductive wire type RF connector 115b can be used, as shown in Figure 1G. Here, the conductive wire RF connector 115a extends through the inner shaft 110b, and the distal portion of the conductive wire RF connector 115a protrudes from the distal end 110d of the inner shaft. The protruding portion of the conductive wire RF connector 115a is positioned within the conduit 119a so that the conductive wire RF connector 115a can connect RF energy to the liquid metal in the conduit 119a, avoiding any discontinuities in the liquid metal and avoiding direct contact with the target airway tissue.

[0035] Alternatively, as shown in Figures 1I and 1J, a ring-shaped connector 115b can be used as shown in Figure 1J. The ring-shaped connector 115b, made from a conductive material, is positioned within a conduit 119a such that the ring-shaped connector 115b transmits RF energy to the liquid metal within the ring-shaped connector 115b without contacting the target airway tissue. Figure 1J shows a cross-sectional view cut at BB in Figure 1H, where the conduit 119a is shown within the ring-shaped connector 115b. In some embodiments, the ring-shaped connector 115b is connected to a conductive wire 116, which is connected to a generator via an inner shaft 110b, as shown in Figure 2E.

[0036] Alternatively, in some embodiments, the ring-shaped RF connector 115b can be mounted on the surface of the distal segment 119, as shown in Figures 2B and 2C. In this example to avoid tissue contact, a preferred embodiment is that the ring-shaped RF connector 115b can be mounted near the distal end of the balloon 120, as shown in Figure 2C, so that when the RF current begins to flow through the liquid metal 150, the ring-shaped RF connector 115b can avoid direct contact with the tissue, as shown in Figure 2G. In some embodiments, the ring-shaped RF connector 115b is positioned at the proximal end of the distal segment 119 in direct proximity to the occluded balloon 120.

[0037] In some embodiments, the ring-shaped RF connector 115b can be positioned recessed in a conduit or cavity 119a to cover a partial surface area of ​​the cavity. Alternatively, the RF connector can be positioned inside the cavity to completely cover the surface area of ​​the cavity. As a further alternative, the ring-shaped RF connector 115b can be positioned inside the cavity and protrude to the outside of the cavity 119a through at least one opening. The ring-shaped RF connector 115b extending from the inside to the outside of the cavity can cover the entire surface area of ​​the cavity, or only a partial surface area of ​​the cavity.

[0038] In some embodiments, the ring-shaped RF connector 115b can be formed on the distal segment 119 of the shaft 110 by at least one conductive metal element. In some embodiments, the at least one conductive element may be formed as a ring segment so as to cover at least one / a certain proportion of the outer circumference of the surface area of ​​the distal segment, or alternatively, as a complete ring so as to cover the entire outer circumference of the partial surface area of ​​the distal segment 119.

[0039] In some embodiments, at least one conductive element may be formed in the shape of a pad or by at least one conductive wire. Furthermore, according to the present invention, the conductive element may be formed by a conductive metal mesh. In some embodiments, a ring-shaped RF connector 115b can be positioned at the proximal end of the distal segment in direct proximity to the inflatable balloon 120.

[0040] In some embodiments, the ring-shaped RF connector 115b can be electrically connected to an RF generator and configured to allow a flow of RF current from the RF generator to the liquid metal. The catheter may further include an RF generator electrically coupled to the ring-shaped RF connector 115b.

[0041] In some embodiments, the flexible shaft 110 may further comprise a guidewire lumen configured to receive a guidewire. In some embodiments, the guidewire may be made from a conductive material so that it can be configured to electrically connect discontinuities in the liquid metal within the target airway.

[0042] Alternatively, the length of the distal inner shaft 110b relative to the inflatable balloon 120 can be made shorter than the length of the distal outer shaft 110a relative to the balloon, so as to form a cavity between the distal end of the outer shaft and the distal end of the inner shaft. The cavity has a distal opening, and the ring-shaped RF connector 115b is placed within this cavity.

[0043] In some embodiments, the inflatable balloon can be mounted on the outer shaft of the inflatable balloon and can be integrally formed with the outer shaft. The distal segment of the flexible shaft includes a cover element that partially overlaps the conductive surface of the ring-shaped RF connector 115b, and the cover element is made of a non-conductive material.

[0044] In some embodiments, the distal segment 119 may include a cover element attached to the distal segment of the shaft to form a cavity having at least one opening, a ring-shaped connector 115b is received within this cavity, and the cover element is made of a non-conductive material.

[0045] In some embodiments, the cover element can be formed as a hollow cylinder that surrounds a portion of the distal segment of the shaft and forms a cavity having at least an opening, the cavity extending from the distal end of the shaft.

[0046] Temperature sensor In one embodiment, the ablation catheter 100 further comprises a temperature sensor 114 configured to read the temperature of liquid metal. The temperature sensor 114 is connected to a thermocouple 117 extending through the inner shaft 110b to the generator, as shown in Figure 2E. In one embodiment, the temperature sensor 114 is positioned within the conduit 119a, as shown in Figures 1H, 1I, 2A, 2D, and 2E, so that the temperature sensor 114 can detect and read the temperature of liquid metal 150 confined within the conduit 119a. Unlike temperature sensors in conventional devices that directly read tissue temperature, the temperature sensor 114 reads the liquid metal itself and returns the value to the generator for temperature control mode operation. In some embodiments that do not utilize conduit space, the temperature sensor 114 is positioned at the distal end of the inner shaft 110b, as shown in Figures 2B-2C.

[0047] Under the generator's temperature control mode, for example, the operator initially sets the temperature to 80°C and monitors the temperature of the activated liquid metal from the temperature sensor 114 for a predetermined time. When the temperature sensor 114 indicates that the activated liquid metal device is above 60°C, the operator can maintain ablation for a predetermined time.

[0048] For accurate readings of the temperature of the activated liquid metal 150 itself during the ablation procedure, the temperature sensor 114 should be positioned away from the tissue. As shown in Figures 2G and 2I, the temperature sensor 114 is configured to be mounted as close to the balloon as possible, or inside the covered portion or conduit 119a, to avoid any direct tissue contact that may indicate tissue temperature.

[0049] In some embodiments, the ablation catheter 100 may further include a temperature sensor mounted on the distal segment 119 of the shaft 110. The temperature sensor 114 may be located within a cavity of the cover element. The temperature sensor may further be formed as a thermocouple embedded in the distal segment of the flexible shaft, with the temperature sensing surface formed as the end face of the distal end of the flexible shaft. In some embodiments, the temperature sensor may be formed as a thermocouple partially mounted on a ring-shaped RF connector 115b so as to form a temperature sensing surface within the area of ​​the ring-shaped RF connector 115b.

[0050] Handle part In one embodiment, the ablation catheter 100 further comprises a handle portion 130 for the operator, as shown in Figures 1A and 1C. The handle portion 130 includes a guidewire port 133, an electrical cable 132, and an injection port 131. The guidewire port 133 is connected to a guidewire lumen 111 for the insertion of a guidewire 135. The electrical cable 132 is connected to a generator 160. The injection port 131 is connected to a fluid channel 112 for fluid communication with a liquid metal device 150. In one embodiment, a syringe is attached to the injection port 131 of the handle portion 130. The syringe contains a small or predefined amount of the liquid metal device 150.

[0051] In an alternative embodiment, the ablation catheter 100 may further include a handle portion located in the distal end area of ​​the flexible shaft 110. The handle portion 130 may include a guidewire port, an electrical connection, and an infusion port. The guidewire port is configured for the insertion of a guidewire and can be connected to a guidewire lumen formed within the flexible shaft. The electrical connection may be configured to connect an RF connector 115 to an RF generator. The infusion port may be formed within the flexible shaft and can be connected to an infusion lumen configured for dripping liquid metal into the passage. The infusion port may be configured for the attachment of a syringe. Such an attachment may be formed, for example, by a Luer connector.

[0052] In some embodiments, the ablation catheter 100 may further include an injection port in an area of ​​the proximal end of the flexible shaft, communicating with a fluid channel of the shaft. In some embodiments, the fluid channel is configured to drip liquid metal supplied to the fluid channel into at least one passage, preferably via the injection port 131. The flexible shaft may further include an expansion lumen, communicating with an inflatable balloon and configured to supply or discharge fluid to and from the inflatable balloon.

[0053] Ablation assembly In one embodiment, an ablation catheter assembly configured to heat a passage includes a liquid metal contained within a syringe. The assembly further comprises an ablation catheter 100 having a flexible shaft having a fluid channel for dripping the liquid metal into the passage, and an RF connector 115 configured to connect RF energy to the liquid metal 150, thereby heating the passage.

[0054] In some embodiments, the ablation catheter assembly comprises the ablation catheter 100 described herein. The assembly further comprises a flexible bronchoscope 170 having an instrument channel (sometimes also called a working channel). As shown in Figure 3, the catheter device 100 is inserted through the instrument channel and advances through the instrument channel. The bronchoscope 170 can be relatively thin to advance deep into the bronchial airway. In some embodiments, the bronchoscope 170 has a diameter of less than 4.0 mm, and in some cases less than 2.0 mm. The bronchoscope 170 may also include other features. In some embodiments, the bronchoscope 170 further comprises a fluid channel for dripping or drawing up liquid metal 150. The ablation assembly may further include an RF generator electrically coupled to the ablation catheter device 100. Finally, the ablation assembly may further include liquid metal 150. In some embodiments, the liquid metal comprises gallium. In some embodiments, the liquid metal is E-GaIn.

[0055] In some embodiments, the bronchoscope 170 may further include a fluid channel configured to drip or draw up fluid through at least one passage at a target site in an internal organ. The ablation catheter assembly may further include a certain amount of liquid metal in electrical contact with the RF connector 115.

[0056] In a further embodiment, the ablation kit comprises an RF ablation catheter or ablation catheter assembly according to a first embodiment of the present invention, and further comprises a container containing liquid metal. The liquid metal may include gallium. The liquid metal can be provided in such a state that it is liquid at 37°C.

[0057] liquid metal To address the requirement of precisely delivering rigid metal electrodes to the center of the target site in peripheral lung lesions, the present invention uses a medical-grade liquid metal device instead of a solid electrode. The liquid metal device acts as an electrode through which RF ablation energy can be applied to the lung tumor. By injecting the liquid metal device into the target site, the liquid metal device adapts to the anatomical structure of the target site. Due to this adapting shape of the liquid metal device, the risk of damage to the surrounding area is reduced. The liquid metal device can be easily removed by suction without damaging the surrounding area. Thus, the liquid metal 150 acts as an independent, flexible electrode within the target site, generating a larger ablation area.

[0058] For the purposes of this specification, a liquid metal device may be described as a device suitable for cancer treatment that includes one or more conductive metals in liquid form to transmit RF energy to a target cancer tumor. A preferred liquid metal is a gallium-based liquid metal. As a metal, the liquid metal has as high conductivity as a metal, high enough thermal conductivity to be used as a thermometer, and excellent radiopaqueness to be used as a radiocontrast agent.

[0059] Furthermore, the liquid metal has a very low melting point (15.5°C), which allows it to maintain its liquid form at room temperature. Due to its excellent radiopaqueness and high viscosity, the injection of liquid metal into the target site of the bronchial tree is completely controllable under fluoroscopic guidance. The injected liquid metal diffuses gradually from proximal to distal without interruption, according to the injected volume and pressure. The operator can control the volume and extent of liquid metal injection based on demand.

[0060] The predefined amount of liquid metal 150 in the syringe can vary depending on the circumstances. In some embodiments, the amount of liquid metal 150 is less than 1.0 ml, in some cases less than 0.5 ml, and in some cases less than 0.2 ml. In some embodiments, the syringe contains at least 0.05 ml of the liquid metal device 150. Most of the injected liquid metal can be removed by bronchoscopy aspirate or spontaneous efflux over several days. Fluoroscopic imaging analysis shows that approximately 82% of the injected liquid metal can be removed by active aspirate or passive efflux. It is noteworthy that the fluidity of the liquid metal is a solution to eliminate specific invasiveness-related problems such as pneumothorax resulting from percutaneous approaches using rigid electrode needles, and problems associated with punctures such as multi-tooth RF needles, which are uncontrollable and cause undesirable damage from misplaced electrodes.

[0061] The liquid metal 150 further comprises one or more conductive metals in liquid form. Examples of liquid metals are gallium, indium, and tin. In some embodiments, the liquid metal 150 comprises gallium. In some embodiments, the liquid metal device 150 comprises indium. In some embodiments, the liquid metal 150 comprises mixtures of liquid metals, such as a combination of gallium, indium, and tin. One such example is "Galinstan," which is an alloy of gallium, indium, and tin. Another example is "eGaIn," which is an alloy of gallium (75.5%) and indium (24.5%).

[0062] In some embodiments, the liquid metal can be heated to a range of 60°C to 80°C by applying an RF current. The liquid metal may contain gallium. The liquid metal can be further provided to be liquid at 37°C. According to a further aspect of the present invention, the liquid metal is delivered into a passage in an internal organ through a catheter. The liquid metal used in various embodiments of the present invention is liquid at body temperature, i.e., 37°C. Preferably, the liquid metal is also liquid at room temperature, i.e., about 25°C.

[0063] Metals are generally defined as materials that can conduct electricity at a temperature of 0 Kelvin. The liquid metal used in this invention is pharmaceutically acceptable, i.e., non-toxic and non-reactive during the time the metal is in use. In one preferred embodiment, the liquid metal contains gallium, which has a melting point of 30°C.

[0064] In a more preferred embodiment, the liquid metal is an alloy. Preferably, the liquid metal is a eutectic alloy. In a further preferred embodiment, the liquid metal is gallium, preferably an alloy containing at least 50% by weight of gallium.

[0065] Gallium can readily alloy with most metals. Therefore, gallium can be used as a component to form many low-melting-point alloys with other metals such as indium (In), bismuth (Bi), tin (Sn), lead (Pb), zinc (Zn), and aluminum (Al). The melting point of the alloy varies depending on the composition and proportions. One embodiment is an alloy containing 62-95% by weight of gallium, 5-22% by weight of indium, and 0-16% by weight of tin.

[0066] EGaIn (78.6 wt% Ga and 21.4 wt% In) and Galinstan® (68.5 wt% Ga, 21.5 wt% In, and 10.0 wt% Sn) are generally available commercially. These are eutectic mixtures. Taking EGaIn as an example, it is produced by placing 78.6 wt% gallium and 21.4 wt% indium in a container, then heating and mixing them using a magnetic stirrer and glass pipette until completely combined. Similar to gallium, bismuth can also include a series of low-melting-point alloys with Pb, Sn, Cd, Zn, and In, etc.

[0067] Target ablation size The target ablation size may depend on the diameter and length of the target airway, as well as the number of branching points in the target airway. For example, it has been shown that a smaller target airway diameter is associated with higher ablation temperatures.

[0068] In some embodiments, the dashed line in Figure 5B defines the target ablation area for RF ablation in the portion of the target airway where the two tumors are located. In some embodiments, the target ablation area may include a mass of alveolar sacs arising from the terminal of the bronchial airway, but may exclude the pulmonary pleura shown in Figure 5B. In some embodiments, the target ablation area may be spherical or oval in shape, for example, the longest diameter of the ablation area may be about 7 cm, the shortest diameter may be about 4 cm, and the longest vertical diameter may be about 5-7 cm.

[0069] Figure 5C shows the computer simulation results for each RF ablation in the same target airway. Figure 5C(a) shows a fluoroscopic image of the liquid metal device filled in the target airway. The fluoroscopic image shows the filling of the bronchial airway and its branches from various angles. In one experiment, the target airway was filled with a preferred liquid metal device, eGaIn, and imaged by fluoroscopy. From these images, a 3D computer model of the eGaIn-filled bronchial airway was generated. From tissue and RF energy modeling, this "tree" was simulated to generate an ablation volume of an oval tissue ablation volume of 7(L) × 4 × 4 cm.

[0070] Figure 5C(b) shows the ablation size when the target airway is not filled with a conductive fluid. Figure 5C(c) shows the ablation size when the target airway is filled with a conductive fluid of NaCl. Figure 5C(d) shows the ablation size when the target airway is filled with a conductive fluid of gold nanoparticles (AuNP). Finally, the ablation size when the target airway is filled with a liquid metal device (E-GaIn). Figure 5D shows that the target airway filled with the liquid metal device has a much larger ablation size.

[0071] treatment The treatment method for ablation of lung tumors uses an approach through the patient's airway. This approach may be called a transbronchial or intrabronchial approach. The airway refers to the anatomical lumen through which air passes, including the trachea, bronchi, and bronchioles. The system for this method may comprise (a) an ablation catheter, (b) a liquid metal device, (c) a bronchoscope or induction sheath, and (d) a generator.

[0072] The treatment method may include inserting a bronchoscope into the target site. The ablation catheter 100 device is advanced through the bronchoscopic working channel to the target airway. The target airway is then closed by inflating an occlusion balloon. Next, a liquid metal device is dripped into the target airway. An RF current is applied to the RF connector 115. This RF current is transmitted through the liquid metal device to deliver tissue ablation RF energy to the tumor. The liquid metal device is drawn up outside the target site. The drawing up of the liquid material device can be done through the bronchoscope.

[0073] As shown in Figure 4A, the ablation catheter 100 can be delivered to a target site as shown in Figures 4A-4B using a flexible bronchoscope 170 (with an outer diameter of 4 mm and a working channel of 2 mm), as described herein. The ablation catheter device 100 is inserted through the instrument channel of the bronchoscope, and the bronchoscope is advanced through the bronchial airway to the target site in the lung. At the target site, the ablation catheter device 100 exits the instrument channel of the bronchoscope and is advanced into the target airway.

[0074] When the ablation catheter is positioned in the proximal portion of the target airway, the occlusion balloon is inflated and locked, as shown in Figures 6A-6B, to create a closed space in the target airway for containing the liquid metal device that will later be injected into the target airway.

[0075] When the target airway is closed, the operator drops the liquid metal device from the syringe into the closed target airway, as shown in Figure 3. The syringe contains various predefined amounts of the liquid metal device, such as 0.5 or 1.0 ml.

[0076] When the operator performs a pressurized injection of a liquid metal device, the device gradually diffuses from the proximal to distal portion of the target airway without interruption, according to the injected volume and pressure. Under fluoroscopic guidance, the operator may be able to control the volume and range of the liquid metal device based on demand. For example, Figure 4D shows that under fluoroscopic guidance, 0.75 ml of liquid metal device is injected into the target airway by the operator. The average volume of liquid metal device in the target airway may be approximately 0.5 ml. However, the average volume can be predetermined based on anatomical variations and tumor location.

[0077] In some embodiments, Figure 6E shows a bronchoscope 170 with the ablation catheter 100 delivered to the bronchioles near the tumor. When the occlusion balloon of the ablation catheter 100 is inflated, the liquid metal device 150 is dripped into the bronchioles. The liquid metal device 150 is delivered out through the fluid channel 112 of the RF ablation catheter device 100. The liquid metal device 100 travels through the bronchioles and their three branches. Once the target site is filled with the liquid metal device 150, the liquid metal device acts as a conformal electrode adjacent to the tumor.

[0078] In this treatment method, the preferred liquid metal for injection is E-GaIn. Because the liquid metal device (i.e., E-GaIn) has suitable radiopaqueness, the device itself can be used as a radiocontrast agent. In addition, the liquid metal device (i.e., E-GaIn) maintains its liquid form at room temperature due to its high viscosity and low melting point (15.5°C). Due to these properties of E-GaIn, the injection of the liquid metal device into the target site is fully controllable under fluoroscopic guidance. In some embodiments, the liquid metal contains gallium.

[0079] By injecting the liquid metal device into the target airway, as shown in Figure 4D, it will adapt to the anatomical structure of the target airway. Due to this adaptable shape of the liquid metal device, it can function as multiple non-traumatic, adaptable RF electrodes. The injected liquid metal device acts as independent, flexible electrodes within the target airway. In addition, the bronchial tree shape of the injected liquid metal device, including twigs as shown in Figure 4D, generates a much larger ablation area than that of a single identical bronchial tree, without its lateral branches. In some embodiments, the dripping step includes dripping the liquid metal into at least two branches of the bronchial airway. In some embodiments, the liquid metal is dripped only into bronchial airways having a diameter of less than 5 mm. In some embodiments, the liquid metal is dripped only into bronchial airways having a length of less than 10 cm.

[0080] When a liquid metal device is injected into a target airway, care may be advised to maintain a distance of at least 5–10 mm between the distal tip of the liquid metal device and the pleura or other internal organs within the sensitive zone to avoid unwanted damage outside the target site. The computer simulation model according to the present invention also supports maintaining a distance between the tip of the liquid metal device and the sensitive zone shown in Figure 4C. Therefore, operators should be aware that injecting a liquid metal device into small airways such as alveoli may be associated not only with a lower chance of removing the liquid metal device after ablation, but also with an increased risk of unwanted damage to the pleura or adjacent organs.

[0081] In some embodiments, the liquid metal device 150 is not dripped into the alveoli of the lung to avoid damage to the alveolar sacs. The amount of liquid metal device 150 may depend on various factors such as the size of the tumor, the location of the tumor, and the number of branches. In some embodiments, the amount of liquid metal device 150 injected is less than 2.0 ml, in some cases less than 1.0 ml, and in some cases less than 0.5 ml. In some embodiments, the liquid metal device 150 is dripped into at least three bronchioles of the bronchial airway, in some cases at least five bronchioles.

[0082] When the liquid metal device is confined within a closed space in the target site, the operator selects a temperature control mode for the RF generator having a desired temperature of 80°C as the ablation mode. Under this ablation mode, the RF connector 115 of the ablation device is configured to allow RF current to pass through the injected liquid metal device so that the liquid metal device delivers radio frequency (RF) energy to ablate the tumor. The temperature sensor of the ablation device is configured to read only the activated liquid metal device and generate an RF ablation feedback loop.

[0083] Under the RF ablation feedback loop, the RF generator continues to deliver RF energy to the injected liquid metal through the RF connector until the temperature reaches 60°C, which is read directly from the injected liquid metal device by a temperature sensor. The effective ablation temperature can be defined as 40°C, 50°C, 60°C, 70°C, or 80°C, depending on the anatomical structure.

[0084] While a wide range of ablation modes are applicable to each procedure, the temperature-controlled mode (set to 80°C) was preferably used in the procedure for consistent and effective ablation. The ablation procedure may be terminated if any of the following conditions are met: (1) the impedance rises above 250 Ω, or (2) the procedure exceeds a predetermined time (5, 10, or 15 minutes, according to a predetermined procedure plan).

[0085] Due to their excellent bioavailability, gallium-based liquid metals have been widely studied in the fields of hyperthermia cancer treatment and prosthetics. For medical applications, E-GaIn can be used in either "bulk material" or "microdroplet" form through ultrasonic fracturing processes. Of these, the microdroplet form, in contrast to the bulk form of E-GaIn, is associated with significant cytotoxic reactions because it leads to the release of high concentrations of gallium and indium ions into the solution.

[0086] In this procedure, bulk-type E-Gain was used, and experiments according to the present invention reaffirmed that, in pigs, even with intentionally excessive amounts of E-Gain, serum gallium and indium concentrations were negligible. This result is consistent with several other studies investigating the direct injection of E-Gain into tumors for hyperthermic cancer treatment.

[0087] Experiments according to the present invention also performed E-Gain biocompatibility testing in accordance with ISO guidelines, and evidence was obtained that E-Gain is safe for intratissue injection. In experiments according to the present invention, a single shot for effective ablation typically requires less than 1 ml of E-Gain. And most of the E-Gain (about 70-90%) can then be directly removed by bronchoscopy or spontaneous exhalation. This remaining amount of bronchial electrode (E-Gain) corresponds to about one-hundredth of the amount of E-Gain for intratumoral injection in these studies, assuming the same body weight. In experiments according to the present invention, the remaining liquid metal device at the target site has not been associated with any significant problems in the lungs. Regarding the toxicity of indium, it is well known that indium is toxic to the lungs, but this only occurs when indium is dispersed in the lungs in the form of an inhaled gas. This is not the case with ablation in this procedure.

[0088] Figure 4E shows the target site, where most of the injected liquid metal is removed by bronchoscopy immediately after the ablation procedure or by spontaneous expulsion over several days, unless the injected liquid metal device is taken up by small airways such as the alveoli. Fluoroscopic imaging analysis suggests that approximately 82% of the injected liquid metal may be removable by active suction or passive expulsion.

[0089] The descriptions and examples provided herein are intended merely to illustrate the invention and not to limit it. Each of the disclosed aspects and embodiments of the invention may be considered individually or in combination with other aspects, embodiments, and variations of the invention. In addition, unless otherwise indicated, the steps of the methods of the invention are not restricted to any particular order of execution. Modifications of the disclosed embodiments that incorporate the spirit and substance of the invention are conceivable to those skilled in the art, and such modifications are within the scope of the invention.

[0090] Unless the context clearly indicates otherwise, the word “or” in this specification is intended to be inclusive and is equivalent to the expression “and / or.” Thus, the expression “A or B” means A or B, or A and B together. Similarly, for example, the expression “A, B or C” means A or B, or C, or any combination thereof.

Claims

1. A radiofrequency (RF) ablation catheter configured to heat a passage in an internal organ which is filled with liquid metal, wherein the ablation catheter A flexible shaft extending between a distal end and a proximal end, wherein the flexible shaft has a fluid channel configured to drop the liquid metal into the passage, An inflatable balloon attached to the aforementioned flexible shaft, RF connector and Equipped with, A portion of the flexible shaft distal to the inflatable balloon is defined as the distal segment of the flexible shaft. An RF ablation catheter in which an RF connector is located in the distal segment and configured to connect RF energy to the liquid metal, thereby heating the passage.

2. The RF ablation catheter according to claim 1, wherein the distal segment has a conduit formed inside the distal segment in such a manner that the conduit transports the liquid metal from the fluid channel.

3. The RF ablation catheter according to claim 2, wherein the RF connector is arranged in the conduit in a recessed manner.

4. The RF ablation catheter according to claim 1, wherein the RF connector is located at the proximal end of the distal segment that is directly adjacent to the inflatable balloon.

5. The RF ablation catheter according to claim 1, wherein the RF connector is a conductive wire connected to an RF generator.

6. The RF ablation catheter according to claim 1, further comprising a temperature sensor attached to the distal segment of the flexible shaft and configured to read the temperature of the liquid metal.

7. The RF ablation catheter according to claim 2, further comprising a temperature sensor attached to the distal segment of the flexible shaft and configured to read the temperature of the liquid metal, wherein the temperature sensor is arranged in a concave manner within the conduit.

8. The RF ablation catheter according to claim 2, wherein the conduit is made of a non-conductive material.

9. The RF ablation catheter according to claim 1, wherein the passage is a bronchial airway of the lung.

10. An ablation catheter assembly configured to heat a passage in an internal organ, wherein the assembly comprises: The liquid metal contained in the syringe, RF ablation catheter, A flexible shaft having a fluid channel for dripping the liquid metal into the passage, An inflatable balloon attached to the aforementioned flexible shaft, RF connector and Equipped with, A portion of the flexible shaft distal to the inflatable balloon is defined as the distal segment of the flexible shaft. An ablation catheter assembly comprising an RF ablation catheter, the RF connector of which is located in the distal segment and configured to connect RF energy to the liquid metal, thereby heating the passage.

11. A flexible bronchoscope comprising a working channel configured for the RF ablation catheter to advance through the fluid channel. The ablation catheter assembly according to claim 10, further comprising the following:

12. The ablation catheter assembly according to claim 10, further comprising an RF generator electrically coupled to the RF connector of the RF ablation catheter.

13. The ablation catheter assembly according to claim 10, wherein the passage is a bronchial airway of the lung.

14. The ablation catheter assembly according to claim 10, wherein the liquid metal comprises gallium.

15. The ablation catheter assembly according to claim 10, wherein the liquid metal is E-GaIn.

16. The ablation catheter assembly according to claim 10, wherein the RF ablation catheter does not use a solid electrode for ablation.

17. The ablation catheter assembly according to claim 10, wherein the distal segment has a conduit formed inside the distal segment in such a manner that the conduit transports the liquid metal from the fluid channel.

18. The ablation catheter assembly according to claim 17, wherein the RF connector is arranged in the conduit in a recessed manner.

19. The ablation catheter assembly according to claim 17, wherein the conduit is made of a non-conductive material.

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