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 is directed generally to devices and methods for ablating lung tumors, and more particularly to ablation treatment of lung tumors using liquid metal as an electrode. [Background technology]

[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 most useful for lung ablation. However, significant technical deficiencies exist in the delivery of RF energy to the lung. The use of multiprong electrodes to increase the total electrode surface area and infusion of ionic fluids have been shown to reduce the impedance to RF current flow in the lung. Although effective, these techniques are not without drawbacks. Fluid infusion is unpredictable and is 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 abnormalities in the ablation zone and increased incidence of pneumothorax.

[0003] In addition, various radio frequency ablation (RFA) techniques have been utilized 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 lung lesions (PPL). In order to ablate tumors closer to the lung periphery, it is desirable for the ablation electrode to be flexible, relatively soft, and small in diameter, preferably conforming to the PPL of less than 2 mm.

[0004] Hyperthermia using radiofrequency (RF) ablation is a treatment for lung tumors, but the requirement to deliver rigid metal electrodes precisely at the center of the target site in peripheral pulmonary lesions often results in risk of damage to surrounding areas or suboptimal ablation. Summary of the Invention

[0005] To solve the problem of the requirement of delivering a rigid metal electrode precisely to the center of the target site, the RF ablation catheter device uses a medical grade liquid metal device instead of using 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 will conform to the anatomical structure of the target site. Due to this conforming shape of the liquid metal device, there is less risk of damage to the surrounding area. The liquid metal device is easily removed by suction without damaging the surrounding area. Thus, 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 with a liquid metal device comprises a flexible shaft configured to advance within a bronchus into the target site. The catheter device further comprises an inflatable balloon mounted on the shaft, with a portion of the flexible shaft distal to the inflatable balloon defined as a distal segment. The catheter device further comprises an RF conductor mounted on the distal segment and configured to allow radio frequency (RF) current to pass through the liquid metal device such that the liquid metal device delivers RF energy to ablate the tumor.

[0007] In one embodiment, a radio frequency (RF) ablation catheter is configured to heat a passageway filled with liquid metal, the ablation catheter comprising a flexible shaft extending between a distal end and a proximal end. The flexible shaft has a fluid channel for dripping liquid metal into the passageway. The ablation catheter further comprises an inflatable balloon mounted on the flexible shaft. The ablation catheter further comprises an RF connector. A portion of the flexible shaft distal to the inflatable balloon is defined as a distal segment of the flexible shaft. The RF connector is disposed on the distal segment and configured to couple RF energy to the liquid metal to heat the passageway.

[0008] In the RF ablation catheter, the distal segment forms a conduit therein in such a manner that the conduit conveys the liquid metal from the fluid channel. In one embodiment, the RF connector is disposed within the conduit in a concave manner. In one embodiment, the RF connector is disposed at a proximal end of the distal segment directly adjacent to the inflation 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 a temperature of the liquid metal. The temperature sensor is disposed within the conduit in a concave manner. The conduit is made of a non-conductive material. Here, the passageway is a bronchial airway of the lung.

[0009] In another aspect, an ablation catheter assembly is configured to heat a passageway, the assembly including a liquid metal contained within a syringe. The ablation assembly further includes an RF ablation catheter comprising a flexible shaft having a fluid channel for dripping the liquid metal into the passageway, and an inflatable balloon attached to the flexible shaft and an RF connector, where a portion of the flexible shaft distal to the inflatable balloon is defined as a distal segment of the flexible shaft, and where the RF connector is disposed on the distal segment and configured to couple RF energy to the liquid metal to heat the passageway.

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

[0011] In the ablation catheter assembly, the RF ablation catheter does not use a solid electrode for ablation. In the RF ablation catheter, the distal segment forms a conduit inside the distal segment in such a manner that the conduit carries the liquid metal from the fluid channel. In some embodiments, the RF connector is disposed in the conduit in a concave manner. In some embodiments, the conduit is made of a non-conductive material.

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

[0013] The method, wherein the passageway is a bronchial airway of a lung. The method further comprises dripping liquid metal into at least two branches of the bronchial airway. The method, wherein the alveoli of the bronchial airway are not filled with liquid metal.

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

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

[0016] In the above method, the amount of liquid metal dispensed is less than 1.0 ml. Also, the liquid metal comprises gallium. In some embodiments, the liquid metal is E-GaIn. In the above method, the liquid metal is dispensed only onto bronchial airways having a diameter less than 5 mm. In some embodiments, the liquid metal is dispensed only onto bronchial airways having a length less than 10 cm. [Brief description of the drawings]

[0017] [Figure 1A] FIG. 1 is a perspective view of an ablation catheter. [Figure 1B] FIG. 1 is a perspective view of an ablation catheter. [Figure 1C] FIG. 2 is a side view of an ablation catheter. [Figure 1D] FIG. 1C is a cross-sectional view taken along line AA in FIG. 1E. [Figure 1E] FIG. 2 is a side view of an occlusion balloon of an ablation catheter. [Figure 1F] FIG. 2 is a cross-sectional view of a flexible shaft. [Figure 1G] FIG. 1F is an enlarged cross-sectional view of the distal portion of FIG. [Figure 1H] FIG. 1C is a cross-sectional view taken along line CC in FIG. 1F. [Figure 1I] FIG. 2 is a cross-sectional view of a flexible shaft. [Figure 1J] FIG. 1B is a cross-sectional view taken along line BB in FIG. [Figure 2A] 1A-1C are cutaway views of different embodiments of the catheter. [Figure 2B]1A-1C are cutaway views of different embodiments of the catheter. [Figure 2C] 1A-1C are cutaway views of different embodiments of the catheter. [Figure 2D] 1A-1C are cutaway views of different embodiments of the catheter. [Figure 2E] 1 is a schematic diagram of a portion of an exemplary catheter. [Figure 2F] 1A-1C show different embodiments of a catheter having a guidewire. [Figure 2G] 1A-1C show different embodiments of a catheter having a guidewire. [Figure 2H] 1A-1C show different embodiments of a catheter having a guidewire. [Figure 2I] 1A-1C show different embodiments of a catheter having a guidewire. [Diagram 3] FIG. 1 illustrates an ablation catheter assembly. [Figure 4A] FIG. 1 illustrates an ablation catheter assembly positioned in the lung. [Figure 4B] FIG. 1 illustrates preferred target sites for pulmonary ablation. [Figure 4C] FIG. 1 illustrates preferred target sites and sensitivity zones. [Figure 4D] FIG. 1 illustrates a target airway filled with liquid metal. [Figure 4E] FIG. 13 illustrates the target airway as the liquid metal is removed. [Figure 5A] FIG. 1 shows targeted ablation sites in peripheral lesions. [Figure 5B] FIG. 1 illustrates 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 unfilled; (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 AuNPs; and (e) shows the ablation size when the target airway is filled with EGaIn. [Figure 5D] FIG. 13 shows a comparison chart illustrating ablation area sizes. [Figure 6A] 1A-1D illustrate steps of an ablation catheter being positioned at a target site. [Figure 6B] 1A-1D illustrate steps of an ablation catheter being positioned at a target site. [Figure 6C] FIG. 13 illustrates the step of dripping liquid metal into the target airway. [Figure 6D] FIG. 13 illustrates the step of dripping liquid metal into the target airway. [Figure 6E] FIG. 13 illustrates the steps of completing the dispensing of liquid metal. [Figure 6F] FIG. 2 illustrates the step of applying an RF current to a liquid metal. [Figure 6G] FIG. 13 shows a situation where the target zone is ablated. [Figure 6H] FIG. 13 shows a situation where the target zone is ablated. [Figure 6I] FIG. 13 is a diagram showing a step of sucking up the dropped liquid metal. [Figure 6J] FIG. 13 is a diagram showing a step of sucking up the dropped liquid metal. [Figure 7A] FIG. 13 is a diagram showing operation parameters and a flow chart. [Figure 7B] FIG. 13 is a diagram showing operation parameters and a flow chart. [Figure 8] FIG. 1 shows exemplary steps of a procedure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] Description of exemplary embodiments To aid in an understanding of the present invention, reference is made to the accompanying drawings which show, for purposes of illustration, specific embodiments in which the invention may be practiced. The drawings herein are not necessarily to scale or to actual proportions. For example, the length and width of components may be adjusted to accommodate the size of a page.

[0019] 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 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 passageway. The ablation catheter further comprises an inflatable balloon mounted on the flexible shaft, a portion of the flexible shaft distal to the balloon is defined as a distal segment of the flexible shaft, the balloon configured to occlude the passageway. The ablation catheter comprises an RF conductor disposed in the distal segment and configured to couple RF energy to the liquid metal to heat the passageway.

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

[0021] Target Airway Also, throughout this disclosure, the target airway or passageway is referred to as the bronchial airway surrounding or adjacent to the target mass within the target site. Note that the target airway includes the main bronchial airway and its branches as shown in FIG. 4D and FIG. 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 the proximal end. In some embodiments, the target airway may have a length of less than 6 cm. The diameter and length of the target airway are closely related to the ablation size, so the preferred target airway may be in the peripheral airway.

[0022] Once the target airway is determined, the operator can determine one of the occlusion balloon locations (i.e., A, B, or C) to be placed in the proximal portion of the target airway as illustrated in the target site in Figure 4B in order to occlude the selected target site. By dripping liquid metal into the occluded target site, the dripped liquid metal can conform 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, ablation catheter 100 includes a flexible shaft 110. Figure 1A shows flexible shaft 110 having an occlusion balloon 120 mounted at a distal portion and a handle portion 130 attached at a proximal portion. Figure 1B shows an enlarged view of the distal portion of shaft 110 showing balloon 120. In one embodiment, the flexible shaft has a length of 50-250 cm.

[0024] In one embodiment, the flexible shaft 110 further comprises an outer shaft 110a and an inner shaft 110b having distal ends 110c and 110d, respectively. The outer shaft 110a has a lumen for insertion of the inner shaft 110b, as shown in FIG. IF. 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 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 cross-section (CC) of FIG. 1G. The guidewire lumen 111 is configured for insertion of a guidewire. In some embodiments, the fluid channel 112 is configured for the passage (i.e., dripping or aspirating) of liquid metal.

[0026] In one embodiment, as shown in Figures 1F and 1G, the distal end 110d of the inner shaft 110b can be configured to have a 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, the conduit 119a preferably creates a channel that is protected or insulated from the target airway tissue so that the liquid metal in the conduit 119 or cavity can avoid discontinuities in the liquid metal and direct contact with nearby airway tissue when RF energy is applied. 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 can be thinned to firmly attach to the inner lumen of the outer shaft 110a while the proximal portion is thinned to create an inflation lumen 113. The inflation lumen 113 is defined as the space between the outer shaft 110a and the inner shaft 110b as shown in FIG. 1F and FIG. 1G for an occlusion balloon 120 mounted on the outer shaft 110a for inflation or deflation of the balloon during a procedure. In some embodiments, a separate inflation lumen 113 can be constructed along the flexible shaft as shown in FIG. 2C-2D. The length and size of the conduit 119a can vary depending on the anatomy of the target airway. In some embodiments, the length of the conduit 119a can be less than 0.5 cm.

[0028] In some embodiments, the flexible shaft 110 can include an inner shaft 110b and an outer shaft 110a, where the outer shaft is disposed surrounding the inner shaft 110b so as to cover at least a partial length of the inner shaft. The flexible shaft 110 extends between a distal end and a proximal end along a shaft axis, 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 the outer shaft 110a, as shown in Figures 1F and 1H. The balloon 120 is positioned within 4-6 mm from the distal end 110c of the outer shaft 110a. In some embodiments, the ablation catheter 100 can have multiple occlusion balloons (not shown) depending on the anatomy of the target airway. In some embodiments, the occlusion balloon can cooperate with other balloons provided on a conventional bronchoscope.

[0030] In one embodiment, the portion of the outer shaft 110a distal to the occlusion balloon 120 can be defined as the distal shaft segment 119 as shown in Figure IB. In some embodiments, the distal shaft segment 119 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 occlusion balloon 120 is to close the entrance of the target airway that is to be filled with liquid metal 150. In some embodiments, the entrance of the target airway may be, for example, about 4-5 mm in diameter. When ablation catheter 100 is positioned in the target airway, balloon 120 is configured to close the entrance of the target airway prior to dripping the liquid metal. After completion of the intended ablation, balloon 120 is deflated and ablation catheter 100 is removed from bronchoscope 170 through the working channel.

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

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

[0034] RF Connectors In one embodiment, the ablation catheter further includes an RF connector 115. The main function of the connector 115 is to couple RF energy to the liquid metal 150 and thereby heat the target airway. Various forms of the RF connector 115 can be used. For example, in one embodiment, a conductive wire type RF connector 115b can be used, as shown in FIG. 1G. Here, the conductive wire RF connector 115a extends through the inner shaft 110b, and a 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 disposed within the conduit 119a such that the conductive wire RF connector 115a can couple the RF energy to the liquid metal in the conduit 119a to avoid any discontinuities in the liquid metal and to avoid 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 of a conductive material is placed in the conduit 119a such that the ring-shaped connector 115b connects RF energy to the liquid metal in 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 in 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 the 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 case of avoiding 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 starts to flow in 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 located at the proximal end of the distal segment 119 directly adjacent to the occlusion balloon 120.

[0037] In some embodiments, the ring-shaped RF connector 115b can be arranged in a recessed manner in the conduit or cavity 119a to cover a partial surface area of ​​the cavity. Alternatively, the RF connector can be arranged in the cavity to completely cover the surface area of ​​the cavity. As a further alternative, the ring-shaped RF connector 115b can be arranged in the cavity and protrude outside the cavity 119a through at least one opening. The ring-shaped RF connector 115b extending from inside the cavity to outside 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 by at least one conductive metallic element on the distal segment 119 of the shaft 110. In some embodiments, the at least one conductive element may be formed as a ring segment to cover at least a / a percentage of the circumference of the surface area of ​​the distal segment, or alternatively, as a complete ring to cover the entire circumference of a partial surface area of ​​the distal segment 119.

[0039] In some embodiments, the at least one conductive element may be formed in the shape of a pad or may be formed by at least one conductive wire. Further, according to the present invention, the conductive element may be formed by a conductive metal mesh. In some embodiments, the ring-shaped RF connector 115b may be located at the proximal end of the distal segment directly adjacent 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 pass a flow of RF current from the RF generator to the liquid metal. The catheter can further comprise an RF generator electrically coupled to the ring-shaped RF connector 115b.

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

[0042] Alternatively, the length of the inner shaft 110b distal to the inflatable balloon 120 can be made shorter than the length of the outer shaft 110a distal to the balloon to form a cavity between the distal end of the outer shaft and the distal end of the inner shaft, the cavity having a distal opening and the ring-shaped RF connector 115b disposed within the 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 overlies the conductive surface of the ring-shaped RF connector 115b, the cover element being made of a non-conductive material.

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

[0045] In some embodiments, the cover element can be formed as a hollow cylinder that surrounds a partial length 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 the liquid metal. The temperature sensor 114 is connected to a thermocouple 117 that extends through the inner shaft 110b to the generator, as shown in FIG. 2E. In one embodiment, the temperature sensor 114 is disposed within the conduit 119a such that the temperature sensor 114 can sense and read the temperature of the liquid metal 150 confined within the conduit 119a, as shown in FIGS. 1H, 1I, 2A, 2D, and 2E. Unlike temperature sensors in prior art devices that directly read tissue temperature, the temperature sensor 114 reads the liquid metal itself and returns a value to the generator for temperature control mode operation. In some embodiments without the use of a conduit space, the temperature sensor 114 is disposed at the distal end of the inner shaft 110b, as shown in FIGS. 2B-2C.

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

[0048] For an accurate reading of the temperature of the activated liquid metal 150 itself during the ablation procedure, the temperature sensor 114 should be placed 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 be indicative of the tissue temperature.

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

[0050] Handle In one embodiment, the ablation catheter 100 further comprises a handle portion 130 for an 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 the guidewire lumen 111 for insertion of a guidewire 135. The electrical cable 132 is connected to a generator 160. The injection port 131 is connected to the fluid channel 112 for fluid communication with the 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 disposed in the area of ​​the distal end of the flexible shaft 110. The handle portion 130 may include a guidewire port, an electrical connection, and an injection port. The guidewire port may be configured for the insertion of a guidewire and may be connected to a guidewire lumen formed in the flexible shaft. The electrical connection may be configured to connect the RF connector 115 to an RF generator. The injection port may be connected to an injection lumen formed in the flexible shaft and configured for dripping liquid metal into the passageway. The injection port may be configured for attachment of a syringe. Such an attachment may be formed, for example, by a Luer connector.

[0052] In some embodiments, the ablation catheter 100 can further include an injection port in the area of ​​the proximal end of the shaft in communication with the fluid channel of the flexible shaft. In some embodiments, the fluid channel is configured to drip liquid metal, which is provided to the fluid channel, into at least one passageway, preferably via the injection port 131. The flexible shaft can further include an inflation lumen in communication with the inflatable balloon and configured to supply or evacuate fluid to / from the inflatable balloon.

[0053] Ablation Assembly In one embodiment, an ablation catheter assembly configured to heat a passageway includes a liquid metal contained in a syringe, and further includes an ablation catheter 100 comprising a flexible shaft having a fluid channel for dripping the liquid metal into the passageway, and an RF connector 115 configured to couple RF energy to the liquid metal 150 to heat the passageway.

[0054] In some embodiments, the ablation catheter assembly comprises an ablation catheter 100 as described herein. The assembly further comprises a flexible bronchoscope 170 comprising an instrument channel (sometimes referred to as a working channel). As shown in FIG. 3, the catheter device 100 is inserted through the instrument channel and advanced through the instrument channel. The bronchoscope 170 can be relatively thin to advance deep within 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 can also include other features. In some embodiments, the bronchoscope 170 further comprises a fluid channel for dripping or siphoning the liquid metal 150. The ablation assembly can further comprise an RF generator electrically coupled to the ablation catheter device 100. Finally, the ablation assembly can further comprise the 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 can further comprise a fluid channel configured to drip or siphon a fluid, preferably into at least one passageway, at a target site in the internal organ. The ablation catheter assembly can further comprise a quantity of liquid metal in electrical contact with the RF connector 115.

[0056] According to a further aspect, an ablation kit comprises an RF ablation catheter or ablation catheter assembly according to the first aspect of the invention, and further comprises a container containing a liquid metal. The liquid metal may comprise gallium. The liquid metal may be provided to be liquid at 37°C.

[0057] liquid metal To solve the problem of the requirement of delivering a rigid metal electrode precisely to the center of the target site in peripheral lung lesions, the present invention uses a medical grade liquid metal device instead of using 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 will conform to the anatomical structure of the target site. Due to this conforming shape of the liquid metal device, there is less risk of damage to the surrounding area. The liquid metal device is easily removed by suction siphoning 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 purpose of more specific definition herein, a liquid metal device may be described as a device suitable for cancer treatment that includes one or more conductive metals in liquid form that transmit RF energy to a target cancer mass. A preferred liquid metal is a gallium-based liquid metal. As a metal, the liquid metal has high electrical conductivity as metals, high enough thermal conductivity to be used as a thermometer, and good radiopacity to be used as a radiocontrast agent.

[0059] Moreover, liquid metal has a very low melting point (15.5°C), which allows it to remain in liquid form at room temperature. Due to its excellent radiopacity and high viscosity, liquid metal injection into the target site of the bronchial tree is fully controllable under fluoroscopic guidance. The injected liquid metal gradually diffuses from proximal to distal without interruption according to the injected volume and pressing force. The operator can control the amount 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 situation. In some embodiments, the liquid metal 150 has a volume of 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 bronchoscopic siphoning or natural expectoration over several days. Fluoroscopic imaging analysis shows that about 82% of the injected liquid metal can be removed by active siphoning or passive expectoration. It is noteworthy that the fluidity of liquid metal is a solution to eliminate certain problems related to invasiveness, such as pneumothorax caused by percutaneous approaches with rigid electrode needles, problems related to punctures, such as multi-tooth RF needles that have poor control and undesirable damage from malpositioned electrodes.

[0061] The liquid metal 150 further includes one or more conductive metals in liquid form. Examples of liquid metals are gallium, indium, and tin. In some embodiments, the liquid metal 150 includes gallium. In some embodiments, the liquid metal device 150 includes indium. In some embodiments, the liquid metal 150 includes a mixture 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 can include gallium. The liquid metal can further be provided to be liquid at 37°C. According to a further aspect of the invention, the liquid metal is delivered into the body organ passageway through a catheter. The liquid metal used in various embodiments of the 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 metals used in the present invention are pharma- ceutically acceptable, i.e., non-toxic and non-reactive during the time of use of the metal. In one preferred embodiment, the liquid metal comprises gallium. Gallium has a melting point of 30°C.

[0064] In a further 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 be easily alloyed with most metals. Therefore, many low melting point alloys can be formed with gallium as an inclusion with other metals such as indium (In), bismuth (Bi), tin (Sn), lead (Pb), zinc (Zn), aluminum (Al), etc. The melting point of the alloy varies depending on the components and proportions. One embodiment is an alloy containing 62-95% by weight gallium, 5-22% by weight indium, and 0-16% by weight 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 commonly and commercially available. They are eutectic mixtures. Taking EGaIn as an example, EGaIn is produced by placing 78.6 wt% gallium and 21.4 wt% indium in a container, then heating and mixing them with a magnetic stirrer and a glass pipette until they are completely mixed. Similar to gallium, bismuth can also include a series of low melting alloys with Pb, Sn, Cd, Zn, 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 branches of the target airway. For example, it has been shown that the smaller the diameter of the target airway, the higher the ablation temperature.

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

[0069] FIG. 5C shows computer simulation results of each RF ablation in the same target airway. FIG. 5C(a) shows x-ray fluoroscopic images of the liquid metal device filled within the target airway. The fluoroscopic images show the filling of the bronchial airway and its branches from various angles. In one experiment, the target airway was filled with the preferred liquid metal device, eGaIn, and imaged by x-ray 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 7 (long) x 4 x 4 cm ovoid shaped tissue ablation volume.

[0070] FIG. 5C(b) shows the ablation size when no conductive fluid is filled in the target airway. FIG. 5C(c) shows the ablation size when the target airway is filled with a conductive fluid of NaCl. FIG. 5C(d) shows the ablation size when the target airway is filled with a conductive fluid of gold nanoparticles (AuNPs). Finally, the ablation size when the target airway is filled with a liquid metal device (E-GaIn). FIG. 5D shows that the target airway filled with the liquid metal device has a much larger ablation size.

[0071] treatment A therapeutic method for ablating lung tumors uses an approach through the patient's airways. The approach may be referred to as a transbronchial or endobronchial approach. The airways refer to the anatomical lumens through which air passes, including the trachea, bronchi, and bronchioles. A system for this method may include (a) an ablation catheter, (b) a liquid metal device, (c) a bronchoscope or introducer 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 bronchoscope working channel to the target airway. The target airway is then closed by inflating the occlusion balloon. A liquid metal device is then instilled into the target airway. RF current is applied to the RF connector 115. The RF current is transmitted through the liquid metal device to provide tissue ablative RF energy to the tumor. The liquid metal device is siphoned out of the target site. The siphoned-up of the liquid material device may be accomplished through the bronchoscope.

[0073] As shown in Figure 4A, an ablation catheter 100 may be delivered to a target site as shown in Figures 4A-B using a flexible bronchoscope 170 (4 mm outer diameter and 2 mm working channel) 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 airways to the target site within the lung. At the target site, the ablation catheter device 100 is advanced out of the instrument channel of the bronchoscope and 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 to make the target airway a closed space for containing a liquid metal device that will later be injected into the target airway, as shown in Figures 6A-6B.

[0075] When the target airway is blocked, the operator drips the liquid metal device from the syringe into the blocked 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 pressurized injection of the liquid metal device, the liquid metal device gradually diffuses from the proximal portion of the target airway to the distal portion without interruption according to the injected amount and the pressing force. The operator may be able to control the amount and range of the liquid metal device based on demand under fluoroscopic guidance. For example, FIG. 4D shows that 0.75 ml of the liquid metal device is injected into the target airway by the operator under fluoroscopic guidance. The average amount of the liquid metal device in the target airway may be about 0.5 ml. However, the average amount may be predetermined based on anatomical variations and mass location.

[0077] In some embodiments, in FIG. 6E, a bronchoscope 170 is shown with an ablation catheter 100 delivered to a truncus bronchiole near a mass. When an occlusion balloon of the ablation catheter 100 is inflated, a liquid metal device 150 is instilled into the bronchioles. The liquid metal device 150 is delivered out of the fluid channel 112 of the RF ablation catheter device 100. The liquid metal device 100 advances into the truncus bronchiole and its 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 mass.

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

[0079] By injecting the liquid metal device into the target airway, it will conform to the anatomical structure of the target airway, as shown in FIG. 4D. Due to this conforming shape of the liquid metal device, the liquid metal device can act as atraumatic conforming multiple RF electrodes. The injected liquid metal device acts as an independent flexible electrode within the target airway. In addition, a bronchial tree shape including branches as shown in FIG. 4D of the injected liquid metal device produces a much larger area of ​​ablation than a single same bronchial tree without its side 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 the liquid metal device is injected into the target airway, care may be advised to distance the distal tip of the liquid metal device at least 5-10 mm from the pleura or other visceral organs in the sensitive zone to avoid unnecessary damage outside the target site. The computer simulation model according to the present invention also supports the distance between the tip of the liquid metal device and the sensitive zone shown in FIG. 4C. Thus, the operator should keep in mind that liquid metal device injection into small airways such as the alveoli may be associated with not only a low possibility of removal of the liquid metal device after ablation, but also an increased risk of undesired pleural or adjacent organ damage.

[0081] In some embodiments, the liquid metal device 150 is not instilled into the alveoli of the lungs 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, the number of branches, etc. 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 instilled into at least three branch bronchiole of the bronchial airway, and in some cases at least five branch bronchiole.

[0082] When the liquid metal device is confined within a closed space within the target site, the operator selects the temperature control mode of the RF generator with a desired temperature at 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 such 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, generating 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 injected liquid metal reaches 60° C., which the temperature sensor reads directly from the injected liquid metal device. The effective ablation temperature can be defined as 40° C., 50° C., 60° C., 70° C., or 80° C., depending on the anatomy, respectively.

[0084] Although a wide variety of ablation modes are applicable in each procedure, a temperature control mode (set at 80° C.) was preferably used in the procedures for consistent and effective ablation. The ablation procedure may be terminated if any of the following conditions exist: (1) impedance rises above 250Ω, (2) a pre-defined time period is reached (5, 10, 15 minutes, according to a pre-defined treatment plan).

[0085] Due to its 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 the form of "bulk material" or "microdroplets" through an ultrasonic disruption process. Among them, the microdroplet form is associated with a greater cytotoxic response, since it leads to the release of high concentrations of gallium and indium ions into solution, in contrast to the bulk form of E-GaIn.

[0086] In this procedure, bulk-type E-GaIn was used, and the present experiments reaffirmed that even with deliberately excessive amounts of E-GaIn, serum gallium and indium concentrations are almost negligible in pigs, a result consistent with several other studies investigating the direct injection of E-GaIn into tumors for hyperthermic cancer treatment.

[0087] The experiments according to the present invention also performed E-GaIn biocompatibility tests according to the instructions of the ISO guidelines, and evidence was obtained that E-GaIn is safe for intra-tissue injection. In the experiments according to the present invention, a single shot for effective ablation usually 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 natural exhalation. This remaining amount of endobronchial electrode (E-GaIn) corresponds to about a few hundredths of the amount of E-GaIn for intratumoral injection in these studies, assuming the same body weight. In the experiments according to the present invention, the remaining liquid metal device at the target site was not 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 inhaled gas. This does not apply to the ablation in this procedure.

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

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

[0090] Unless the context clearly indicates otherwise, the word "or" herein is intended to be inclusive and is equivalent to the term "and / or." Thus, the term "A or B" means A, or B, or both A and B. Similarly, for example, the term "A, B, or C" means A, or B, or C, or any combination thereof.

Claims

1. 1. A radio frequency (RF) ablation catheter configured to heat a liquid metal-filled passageway, the ablation catheter comprising: a flexible shaft extending between a distal end and a proximal end, the flexible shaft having a fluid channel configured to drip the liquid metal into the passage; an inflatable balloon attached to the flexible shaft; An RF connector; Equipped with a portion of the flexible shaft distal to the inflatable balloon is defined as a distal segment of the flexible shaft; An RF ablation catheter, wherein an RF connector is located in the distal segment and configured to couple RF energy to the liquid metal to heat the passageway.

2. The RF ablation catheter of claim 1 , wherein the distal segment forms a conduit therein such that the conduit conveys the liquid metal from the fluid channel.

3. The RF ablation catheter of claim 2 , wherein the RF connector is disposed within the conduit in a concave manner.

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

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

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

7. The RF ablation catheter of claim 2 , wherein the temperature sensor is disposed within the conduit in a recessed manner.

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

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

10. 1. An ablation catheter assembly configured to heat a passageway, the assembly comprising: a liquid metal contained within a syringe; 1. An RF ablation catheter comprising: a flexible shaft having a fluid channel for dripping the liquid metal into the passage; an inflatable balloon attached to the flexible shaft; An RF connector; Equipped with a portion of the flexible shaft distal to the inflatable balloon is defined as a distal segment of the flexible shaft; an RF ablation catheter, wherein an RF connector is located at the distal segment and configured to couple RF energy to the liquid metal to heat the passageway.

11. a flexible bronchoscope comprising a working channel configured for advancing the ablation catheter through the fluid channel; The ablation catheter assembly of claim 10 further comprising:

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

13. The RF ablation catheter of claim 10 , wherein the passageway is a bronchial airway of the lung.

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

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

16. The ablation catheter assembly of claim 10 , wherein the RF ablation catheter does not use solid electrodes for ablation.

17. The RF ablation catheter of claim 10 , wherein the distal segment forms a conduit therein such that the conduit conveys the liquid metal from the fluid channel.

18. The RF ablation catheter of claim 10 , wherein the RF connector is disposed within the conduit in a concave manner.

19. The RF ablation catheter of claim 10 , wherein the conduit is made of a non-conductive material.

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