Cryotherapy systems and methods for targeted pulmonary neuromodulation therapy

Abstract

Disclosed herein are cryotherapeutic devices for targeted lunch neuromodulation therapy, and associated systems and methods. A cryotherapeutic device configured in accordance with embodiments of the present technology may include, for example, an elongate shaft having a distal portion and a cooling assembly positioned at the distal portion. The shaft is configured to deliver the distal portion to a target site within a bronchial tube of a patient. The cooling assembly includes an expandable member, an injection chamber configured to discharge refrigerant into the expandable member, and a discharge lumen configured to receive expanded refrigerant. The cooling assembly is configured to impart cryogenic cooling to ablate nerve fibers proximate the target site. The device may be sized to fit within a working channel of a bronchoscope such that at least a portion of the cooling assembly may be visualized during a cryotherapeutic procedure.

Description

[0001] Cross - Reference to Related Applications

[0002] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 417,964, entitled "MONITORING SYSTEMS AND METHODS FOR TARGETED LUNCH DENERVATION THERAPIES", filed on October 20, 2022, the entire content of which is incorporated herein by reference. Technical Field

[0003] The present technology generally relates to targeted neuromodulation in the lungs. Some embodiments are directed to cryotherapy devices, systems, and methods for targeted lung neuromodulation. Background Art

[0004] Lung diseases are characterized by pathologies that adversely affect lung performance, making it difficult for an animal (e.g., a human) that breathes air to perform the gas exchange necessary for survival. Certain lung diseases, such as chronic obstructive pulmonary disease ("COPD"), asthma, and bronchiectasis, particularly affect the airways that carry oxygen into the body. For example, COPD and asthma are characterized by narrowed or blocked airways, which may be the result of thickening of the airway wall, structural changes within or around the airway wall, or a combination thereof. For example, obstruction of the airway lumen can be caused by excessive intraluminal mucus and / or edema fluid. Thickening of the airway wall can be caused by inflammation, contraction, or hypertrophy of airway smooth muscle, mucus gland hypertrophy, and / or edema. Structural changes around the airway can reduce the radial traction on the airway wall and lead to airway narrowing. Such narrowing or obstruction of the airway can significantly reduce the amount of gas exchanged in the lungs, resulting in dyspnea.

[0005] COPD is characterized by airflow limitation and chronic respiratory symptoms, such as shortness of breath and coughing. The two most common types of COPD are emphysema and chronic bronchitis. Emphysema is defined as enlarged air spaces (alveoli) with ruptured walls, resulting in permanent damage to lung tissue. Chronic bronchitis is defined as coughing up sputum (i.e., producing mucus or phlegm) for at least three months within two years. Brief Description of the Drawings

[0006] Figure 1A is a partial schematic view of a cryotherapy system configured according to an embodiment of the present technology.

[0007] Figure 1B is Figure 1A an enlarged side view of a cryotherapy device of the cryotherapy system of

[0008] Figure 1C is configured according to an embodiment of the present technology Figure 1B an enlarged partial cross - sectional view of the distal portion of the cryotherapy device of

[0009] Figure 2 It is an enlarged view of a part of an injection tube for a cryotherapy device configured according to an embodiment of the present technology.

[0010] Figure 3 It shows a treatment position of a cryotherapy procedure according to some embodiments of the present technology.

[0011] Figure 4 It shows an end - view image of a cooling assembly of a cryotherapy device in an airway during various stages of a cryotherapy procedure according to some embodiments of the present technology.

[0012] Figure 5 It is a block diagram of a processing device configured to execute control of a cryotherapy system according to some embodiments of the present technology.

[0013] Figure 6A It is a side view of a distal portion of a cryotherapy device configured according to some embodiments of the present technology.

[0014] Figure 6B It is a side view of a distal portion of a cryotherapy device configured according to some embodiments of the present technology.

[0015] Figure 7 It is a flowchart of a method for cryo - modulating a nerve according to some embodiments of the present technology.

[0016] Figure 8 It shows a monitoring component in a vasculature positioned around a target site during a cryotherapy procedure according to an embodiment of the present technology. Detailed Description

[0017] This disclosure relates to cryotherapy systems and methods for targeted pulmonary neuromodulation. In some embodiments, for example, a cryotherapy system can include a cooling assembly (also referred to as an “end effector”) at a distal portion of a shaft for performing cryotherapy procedures at one or more target sites within a pulmonary airway to modulate nerves (e.g., ablation, denervation) to treat COPD and / or other pulmonary diseases. In various embodiments, the cooling assembly can include an expandable member that receives a refrigerant in a manner adapted to deliver cryotherapy cooling to the target site. The cooling assembly can be operably coupled to a control assembly that sends and receives signals to control the operation of the refrigerant to the cooling assembly. In some embodiments, the delivery and / or discharge of the refrigerant from the cooling assembly is based on one or more intraoperative signals associated with feedback from the cryotherapy system. The (one or more) intraoperative signals can provide feedback on various parameters at or around the target site (also referred to as the treatment location) such that cryotherapy can be performed in response to the provided parameters. In some embodiments, the cryotherapy device can be configured to be used with a bronchoscope during a cryotherapy procedure such that a user (e.g., a physician performing the procedure) can visualize the target site before, during, and / or after the procedure.

[0018] Existing treatments for pulmonary disorders include the use of systemic or inhaled medications, such as aerosol delivery of corticosteroids, antibiotics, bronchodilators, “mucolytic” agents (e.g., water, hypertonic saline solution). Many of these medications have severe side effects. Thermal ablation treatments, such as bronchial thermoplasty, as another treatment option, involve disrupting smooth muscle tone by ablating the airway wall in the intrapulmonary bronchial branches, thereby eliminating smooth muscle and nerves in the pulmonary airway wall. The treated airways may not respond to inhaled irritants, systemic hormones, as well as local and central nervous system inputs. Thus, this disruption of smooth muscle tone and nerves in the airway wall may thus adversely affect pulmonary performance. The present technique has been shown to cryoablate nerve fibers for treating COPD and / or other respiratory diseases while maintaining smooth muscle tone and avoiding the systemic effects of medications.

[0019] Reference is made below to Figures 1A - 8Describe the specific details of several embodiments of the present technology. Although many embodiments are described below regarding implant devices, systems, and methods for treatment and monitoring during cryotherapy for treating COPD, other applications and other embodiments in addition to those described herein are also within the scope of the present technology. For example, the present technology can be used to treat different indications (e.g., asthma) and / or different target sites in a patient's body other than the airways, such as other parts of the respiratory system and / or other parts of the body. Additionally, several other embodiments of the present technology can have different configurations, components, or procedures from those described herein, and the features of the illustrated embodiments can be combined with each other. Thus, one of ordinary skill in the art will accordingly understand that the technology can have other embodiments with additional elements, or that the technology can have other embodiments that do not have several of the features shown and described below with reference to the accompanying drawings.

[0020] Regarding the terms "distal" and "proximal" in this specification, unless otherwise stated, these terms can refer to the relative positions of parts of a cryotherapy device and / or an associated delivery device with respect to the position of an operator and / or within the bronchus. For example, proximal can refer to a position closer to the operator of the device or an associated entry point (e.g., the mouth), and distal can refer to a position farther from the operator of the device or farther from the entry point.

[0021] Bronchial neuromodulation

[0022] Bronchial neuromodulation is the partial or complete disablement or other effective disruption of the nerves that innervate parts of the bronchus. In particular, bronchial neuromodulation includes inhibiting, reducing, and / or blocking neural communication along the nerve fibers (i.e., efferent and / or afferent nerve fibers) that innervate a selected bronchus. Such disablement can be long-term (e.g., permanent or for a period of months, years, or decades) or short-term (e.g., for a period of minutes, hours, days, or weeks). Bronchial neuromodulation is expected to effectively treat several clinical conditions characterized by increased activity of airway smooth muscle and mucus-producing glands within the airways, such as COPD. Neuromodulation is expected to relax airway smooth muscle, reduce mucus production, and / or reduce nervous system-mediated inflammation and edema, which results in a reduction in airway obstruction and makes it easier to breathe.

[0023] As disclosed herein, cryotherapy can be used to partially or completely disable neural pathways (such as those innervating the bronchi). Cryotherapy involves cooling the tissue at the target site in a manner that modulates neural function. The mechanisms of cryotherapy-induced tissue injury include, for example, direct cell injury (e.g., necrosis) and sublethal hypothermia followed by apoptosis. Exposure to cryotherapy cooling can cause acute cell death (e.g., immediately after exposure) and / or delayed cell death (e.g., during tissue thawing and subsequent reperfusion). Some embodiments of the present technology include cooling structures at or near the inner surface of the wall of the airway such that adjacent (e.g., neighboring) tissue is effectively cooled to the depth at which nerves innervating the lung (e.g., the phrenic nerve) are located. For example, the cooling structure is cooled to an extent that it causes therapeutically effective cryoneurolysis. It is expected that sufficient cooling of at least a portion of the nerve will slow or potentially block the conduction of nerve signals to produce an extended or permanent reduction in neural activity.

[0024] Cryotherapy has certain characteristics that can be beneficial for intratracheal neuromodulation. For example, rapid tissue cooling provides an analgesic effect such that cryotherapy can be less painful than ablating tissue at elevated temperatures. Thus, compared to thermal ablation procedures, cryotherapy may require less analgesic medication to maintain patient comfort during the procedure. Additionally, reduced pain reduces patient movement, thereby increasing operator success and reducing surgical complications. Cryotherapy also generally does not cause significant collagen tightening and thus cryotherapy is generally not associated with airway stenosis.

[0025] Cryotherapy is typically operated at a temperature that causes the cryotherapy applicator to adhere to the tissue. This can be beneficial as it promotes stable, consistent, and continuous contact with the tissue along the inner wall of the bronchus during treatment. The typical treatment conditions can make this an attractive feature as, for example, breathing causes the bronchi to move up and down, thereby moving the target site, the patient can move during treatment, and / or the catheter associated with the cryotherapy applicator can move. Additionally, during the process of asking the patient to hold their breath to keep the target site stationary, once the applicator adheres to the target site, the patient can exhale. This reduces the duration of breath-holding, which can often be difficult for those patients with COPD or other pulmonary diseases being treated with this procedure. Adhesion associated with cryogenic cooling can also be advantageous when treating short bronchi where it may be more difficult to achieve stable intraluminal positioning.

[0026] Alternative embodiments of cryotherapy systems and methods

[0027] Figure 1A is a partial schematic view of a cryotherapy system 100 (also referred to as "cryotherapy system 100" or "system 100") configured according to an embodiment of the present technology.Figure 1B is Figure 1A an enlarged side view of cryotherapy device 130 of system 100, and Figure 1C is Figure 1A and 1B an enlarged partial cross-sectional view of cryotherapy device 130. Referring Figure 1A , system 100 may include a console 102 operably coupled to cryotherapy device 130. Console 102 may include a supply component 104 (schematically shown, also referred to as "refrigerant source") that holds a refrigerant at a desired pressure, such as liquid nitrogen (N2O), carbon dioxide, and / or hydrofluorocarbons ("HFC", e.g., R-410A, etc.). Supply component 104 may be in fluid communication with cryotherapy device 130 via a supply line 106 (e.g., lumen, tube) to deliver the refrigerant to cryotherapy device 130. A discharge line 108 (e.g., lumen, tube) may also be coupled to cryotherapy device 130 to receive the evaporated refrigerant (e.g., nitrogen) after the refrigerant expands during a cryotherapy procedure. In some embodiments, discharge line 108 is coupled to a pump (not shown, e.g., a vacuum pump) and / or a control valve at console 102 to suction the evaporated refrigerant from cryotherapy device 130. This reduces the back pressure of the evaporated refrigerant and, in combination with the supply flow rate, may increase the refrigeration power.

[0028] Referring together Figure 1A and Figure 1B , cryotherapy device 130 includes a shaft 132 having a proximal portion 134 and a distal portion 136, a handle 138 at proximal portion 134, and a cooling assembly 140 at distal portion 136 of shaft 132. Supply line 106 may be in fluid communication with a delivery lumen 133 extending through shaft 132 to deliver the refrigerant to cooling assembly 140, and discharge line 108 may be in fluid communication with a discharge lumen 135 extending through or beside shaft 132 to receive the refrigerant from cooling assembly 140. In some embodiments, supply line 106 and discharge line 108 define delivery lumen 133 and discharge lumen 135. Shaft 132 is configured to position distal portion 136 at a treatment site in an airway, the treatment site being near (e.g., therein or nearby) a desired site within a bronchus, and cooling assembly 140 is configured to deliver a therapeutically effective cryoneurolysis to the target site. Shaft 132 may apply cryogenic cooling (e.g., at a temperature of -100°C to -255°C, -90°C, or other suitable temperature) for therapeutically effective neurolysis at one or more target sites within a bronchus, with the expectation of alleviating symptoms of various respiratory diseases (such as COPD) and / or treating various diseases.

[0029] In some embodiments, the cryotherapy device 130 is configured to be used with a bronchoscope 160, which can be used to visualize a target site and facilitate delivery of the cooling assembly 140 to the target site within the bronchus. For example, a distal portion of the bronchoscope 160 can be inserted into the nose or mouth of a subject (e.g., a human patient), and a distal portion 136 of the shaft 132 can pass through the working channel 162 of the bronchoscope 160 to navigate the cooling assembly 140 to a location at or near the target site. The cooling assembly 140 can then be exposed from the bronchoscope 160 (e.g., by moving the shaft 132 distally relative to the distal opening of the working channel 162 or retracting the bronchoscope 160, and the cooling assembly 140 can then deliver cryogenic therapy cooling to the tissue at the target site). In such an embodiment, the bronchoscope 160 can provide direct visualization to guide the cooling assembly 140 to one or more desired locations within the airway, as well as provide visualization during and / or after cryogenic therapy cooling. Suitable bronchoscopes 160 can include, but are not limited to, those manufactured by Olympus Corporation of Center Valley, Pennsylvania, USA.

[0030] The supply component 104 can include a single-use refrigerant cartridge for storing refrigerant under pressure and / or a larger container (e.g., a tank, a refillable cylinder, etc.) that holds a sufficient volume of refrigerant to perform multiple cryotherapy procedures. The refrigerant contained within the supply component 104 can be liquid nitrogen, carbon dioxide, hydrofluorocarbons (“HFCs,” e.g., R-410A, etc.) and / or other suitable compressed or condensed refrigerants that can be held within the supply component 104 at a high enough pressure to keep the refrigerant at least substantially liquid at ambient temperature. The supply component 104 is configured to maintain the refrigerant at a desired pressure. For example, in one embodiment, liquid N2O is contained within the supply container 104 at a pressure of 750 psi or greater, such that it is at least substantially liquid at ambient temperature. In other embodiments, the refrigerant can include. For example, when the refrigerant is liquid N 2At time O, the supply component 104 can hold the refrigerant at a pressure of 750 psi (5,171.07 kPa) or greater to keep the refrigerant in at least substantially a liquid state at ambient temperature. In some embodiments, the supply component 104 can include one or more chambers (e.g., tanks, containers) that receive the refrigerant emissions (e.g., nitrogen) generated during cryotherapy. The supply component 104 can include features such as one or more valves that are configured to control the flow of refrigerant from the supply component 104 to the cooling assembly 140 at the distal portion 136 of the cryotherapy device 130. A flow sensor can be included in or coupled to the supply component 104, the supply line 106, and / or the discharge line 108 to sense or measure the flow of refrigerant to and / or from the cryotherapy device 130. As Figure 1A shown, the supply component 104 is housed within or otherwise carried by the console 102 and is coupled to the shaft 132 of the cryotherapy device 130 via an umbilical 103. In some embodiments, the supply component 104 can be separated from the console 102.

[0031] As Figure 1A further shown, the system 100 can also include a control component 110, such as a computing device, that receives information, data, signals, and / or other feedback from the various components of the system 100 and, in some embodiments, provides the detected information to the operator before, during, and / or after the cryotherapy procedure. For example, the control component 110 can include a display 112 that provides information related to the refrigerant delivery rate, the discharge rate, the temperature, the imaging (e.g., from the bronchoscope 160), the position information, the patient vital signs, the timer, and / or other information associated with the cryotherapy procedure and / or the patient. The display 112 can be a monitor, a touch screen, an LCD display, and / or other types of devices that convey information to those devices associated with the procedure. In some embodiments, the control component 110 is configured to transmit information associated with the procedure to one or more remote devices (e.g., laptop computers, tablet computers, databases) in the operating room and / or at a remote location (e.g., via Bluetooth, Wi-Fi, Ethernet, etc.).

[0032] In various embodiments, the control component 110 may also be configured to generate control signals that control the delivery of refrigerant from the supply component 104, control the operation of the cryotherapy device 130, and / or send / receive signals from the cryotherapy device 130 and / or other devices associated with the cryotherapy procedure (e.g., patient vital signs, bronchoscope 160, sensors) to control other components of the system 100. For example, during a cryotherapy procedure, the control component 110 may control the operation of the cryotherapy device 130 to initiate, maintain, adjust, pause, stop, and / or resume the delivery of refrigerant to the treatment site of the subject in response to user input and / or intraoperative signals (e.g., detected from sensors associated with the system 100).

[0033] In Figure 1A the illustrated embodiment, the console 102 is a single unit that includes the control component 110 and the supply component 104. For example, the console 102 may include a cart (e.g., including wheels) that carries the control component 110, the supply component 104, and / or other components of the system 100 such that the components can be transported together to a suitable location (e.g., different operating rooms, different locations within an operating room) between and / or during cryotherapy procedures. In other embodiments, the components of the console 102 may be separated from each other. For example, the supply component 104, the control component 110, and / or the display 112 may be operably connected but separated from each other. In some embodiments, the bronchoscope 160 is operably coupled to a console and / or a separate display that is separate from the console 102 such that imaging from the bronchoscope 160 is provided on the separate display.

[0034] Now refer to Figure 1B and Figure 1C , the cooling assembly may include an expandable member 142, such as a balloon, attached to the distal portion 136 of the elongate shaft 132, and an injection tube 144 extending from the shaft 132 into the expandable member 142. The injection tube 144 may be in fluid communication with the supply line 106 ( Figure 1A ) and the refrigerant supply component 104 ( Figure 1A)Fluidly connected to deliver refrigerant to the chamber defined by the expandable member 142. For example, the injection tube 144 may include one or more openings 146 selectively positioned along the injection tube 144 to discharge the refrigerant to a desired location and / or a selected portion within the expandable member 142. In some embodiments, the refrigerant may be delivered at a pressure between 200 psi and 760 psi and / or other suitable pressures. The internal chamber of the cooling assembly 140 may also be in fluid communication with a refrigerant discharge lumen port 148 at the distal portion of the discharge lumen 135 to remove refrigerant from the expandable member 142. In the illustrated embodiment, for example, the discharge lumen 135 is larger in size than the injection tube 144 and extends around the proximal portion of the injection tube 144 such that the gap between the injection tube 144 and the inner wall of the discharge lumen 135 defines the discharge port 148. The injection tube 144 and the discharge lumen 135 and the associated port 148 may be sized or configured relative to each other based on one or more factors including the desired flow rate and / or pressure of fresh refrigerant to the target site, the desired flow rate and / or pressure of the refrigerant discharge removed from the target site, the degree of expansion of the fresh refrigerant at the target site, combinations thereof, and / or other suitable factors. In some embodiments, for example, the discharge shaft may have an outer diameter of 2.3 mm. In some embodiments, the discharge lumen 135 may discharge the refrigerant at a high rate (e.g., 3,000 - 6,000 sccm) to cause the refrigerant to cycle rapidly through the expandable member 142. In other embodiments, the discharge shaft dimensions and / or discharge rate may be different.

[0035] The elongate shaft 132, the delivery lumen 133, and / or the discharge lumen 135 may be made of a material that is substantially inert to the refrigerant, substantially inserted into and biocompatible with the physiological environment of the airway, and / or has sufficient flexibility at or near the temperature of the refrigerant discharge. In some embodiments, for example, the elongate shaft 132 may be made of a multi-layer braided thermoplastic elastomer material (e.g., thermoplastic polyurethane, thermoplastic copolyester (e.g., PEBAX)) and may have an outer diameter of 0.09 inches (or 2.3 mm). The delivery lumen 133 and / or the injection tube 144 may be made of a material that is substantially inert to the refrigerant, substantially inert to and biocompatible with the physiological environment of the airway, and / or has sufficient flexibility at or near the temperature of the fresh refrigerant or refrigerant discharge to deliver to a target site in the airway while maintaining the pressure of the fresh refrigerant or refrigerant discharge and the pressure and / or temperature drop during injection of the fresh refrigerant. For example, the injection tube 144 may be made of Nitinol. In various embodiments, the shaft 132 and / or the injection tube 144 may be made of other suitable materials and / or have different dimensions suitable for delivery to the target site.

[0036] The inflatable member 142 can have two configurations: a delivery state and an inflated state (as Figure 1B and Figure 1C shown). In the delivery state, the inflatable member 142 can have a low profile (e.g., deflated) to facilitate its movement through the airway before and / or after cryotherapy cooling. For example, when extending the cooling assembly 140 beyond the distal end of the bronchoscope 160 ( Figure 1A ) to a position for cryotherapy cooling (e.g., by delivering pressurized liquid nitrogen with low temperature and high pressure) to reach a target site or near the target site, and / or when retracting the inflatable member 142 and the injection tube 144 into the distal end of the bronchoscope 160 after the treatment is completed to remove the cooling assembly 140 from the target site. In the deflated configuration, the inflatable member 142 can be at least partially retracted into the elongate shaft 132 (or bronchoscope 180).

[0037] In the inflated state, the inflatable member 142 is inflated (e.g., via a lumen in internal communication with the inflatable member 142) or otherwise expanded to define an internal chamber adapted to receive a refrigerant. For example, the inflatable member 142 can be positioned outside the distal end of the bronchoscope 160 such that it is positioned at the target site and inflated to abut and / or press against adjacent tissue of the airway. When fresh refrigerant is delivered from the injection tube 144 to the inflatable member 142 via one or more openings 146, for example, in the injection tube 144, the refrigerant undergoes rapid expansion due to the pressure drop, thereby changing from a liquid to a gas and achieving rapid cooling of the surrounding tissue for cryoablation neuromodulation. The refrigerant continues to be delivered into the inflatable member 142, and thus the already expanded refrigerant is discharged through the discharge port 148 and guided away from the target site via the discharge lumen 135.

[0038] In the inflated configuration, the inflatable member 142 can expand radially to conform to the shape of the airway such that the refrigerant can contact or be in close proximity to the target site on the airway wall.

[0039] The size and shape of the expandable member 142 can be designed such that when in the expanded state, the expandable member 142 can be opposed to the inner wall of the adjacent airway section to fix the expandable member 142 in place. For example, the expandable member 142 can be configured to circumferentially juxtapose the inner wall of the airway at a cross-section. Additionally, the expandable member 142 can be made of a compliant and / or semi-compliant material that allows the expandable member to fit within a variety of different airway sizes while also at least partially conforming to the inner wall of the airway to press against or abut tissue. For example, the size of the expandable member 142 can be designed to have a maximum outer diameter of 15 mm - 10 mm and / or other diameters therebetween. In some embodiments, the expandable member 142 can be used to fully press against and treat an airway lumen with a diameter of 12 - 15 mm, which is typical of the left lower lobe bronchus and the right middle lobe bronchus, and / or a lumen as small as 9 mm (e.g., typical of the right upper lobe bronchus). In some embodiments, the expandable member can treat smaller or larger airway lumens. The expandable member 142 can also be made of a material that provides and can withstand rapid heat transfer to allow cryogenic cooling of adjacent and surrounding tissue. The material can be substantially inert to and biocompatible with the physiological environment of the airway and / or maintain the temperature of the refrigerant discharged from the injection tube 144 at which cryotherapy is performed. For example, the expandable member 142 can be made of polyurethane, polyethylene, polytetrafluoroethylene (PTFE), polyvinyl chloride (PVC), nylon, nylon elastomer, silicone, polyimide, polypropylene, etc. or a combination thereof.

[0040] One or more openings 146 along the injection tube 144 can be located at selected positions along the length and / or circumference of the injection tube 144 to provide a desired cryoablation pattern. For example, the openings 146 can be oriented in a manner that produces one or more fully circumferential lesions at a cross-section of 360°. The cryoablation pattern can be further enhanced by delivering the refrigerant from the injection tube 144 substantially uniformly in the circumferential direction along a desired cross-section. This can be achieved, for example, by arranging the openings 146 substantially uniformly in the circumferential direction on the injection tube 144. Figure 2 Examples of the openings 146 arranged in a pattern along the injection tube 144 are provided. In some embodiments, the openings 146 are oriented in a manner that provides cryoablation along a non-fully circumferential cross-section (e.g., a hemispherical portion of the airway, spaced-apart regions along the length or radial portion of the airway).

[0041] As another example, when denervation via cryoablation involves creating one or more lesions that are less than 360° at any cross-section, the expandable member 142 may present a non-occlusive cross-section such that the cross-section of the expandable member 142 contacts only a portion of the circumferential segment of the inner wall at any cross-section of the airway. For example, the expandable member 142 may have a non-occlusive and eccentric cross-section that is configured to form a linear, curved, or helical-shaped ablation on a section of the airway. When the expandable member 142 is in the expanded configuration, the non-occlusive expandable member 142 may allow for lung ventilation, mucus clearance, positioning of devices (e.g., guidewires, mucus clearance devices), etc. or a combination thereof.

[0042] As Figure 1C Further shown as in, the cooling assembly 140 may include a non-invasive tip portion 150 that is circular or otherwise shaped to provide a non-invasive front surface of the cooling assembly 140. The tip portion 150 may also or alternatively provide a support structure to which the distal portion of the injection tube 144 and / or the distal portion of the expandable member 142 is supported or otherwise fixed.

[0043] In some embodiments, the cooling assembly 140 may include one or more sensors 154 that detect one or more parameters within the cooling assembly 140. For example, the sensor 154 may be a thermocouple that measures the temperature within the expandable member 142. This information may be transmitted to the console 102 ( Figure 1A ) such that the operator can track the temperature and confirm that the desired cooling temperature is met. In some embodiments, the sensor 154 may measure the pressure within the expandable member 142, the flow rate of the effluent, the flow rate of the injection tube 144, and / or other parameters.

[0044] In various embodiments, the cooling assembly 140 may also include valves, such as needle valves, Joule-Thomson throttle valves, throttle valve elements, etc., for providing a pressure drop and a lower downstream temperature, thereby altering and / or enhancing the effectiveness and / or efficiency of cryoablation. For example, a Joule-Thomson throttle valve may recover work energy from the expansion of the refrigerant, resulting in a lower downstream temperature.

[0045] As Figure 1C Further shown as in, the cooling assembly 140 may include one or more radiopaque markers 152 positioned along the injection tube 144 to allow for position guidance. In other embodiments, the radiopaque markers 152 may be positioned at other locations on the cooling assembly 140, such as on the expandable member 142 and / or along the shaft 132.

[0046] As Figure 1BAs shown, the shaft 132 may also include a balloon protector assembly 137 that extends over and / or adjacent to the expandable member 142 to protect components of the cooling assembly 140 as the cooling assembly 140 is moved into and out of the bronchoscope 160( Figure 1A ). The protector assembly 137 may further impart stiffness to the distal portion 136 of the shaft 132.

[0047] In some embodiments, the injection tube 144 may include an outer tube and a delivery sheath in which the refrigerant delivery holes 146 are located. The delivery sheath may extend beyond the injection tube 144 or retract into the injection tube 144. The number (or count) of refrigerant delivery holes 146 operable to disperse refrigerant into the interior of the expandable member 142 may be adjusted by adjusting the length by which the delivery sheath extends beyond the outer tube of the injection tube 144. In some embodiments, the delivery sheath may be rotatable such that the direction in which the refrigerant is ejected into the expandable member 142 may be adjusted by rotating the delivery sheath. The adjustment of the delivery sheath (e.g., rotation, extension, or retraction) may be controlled at the handle 138( Figure 1B ) and / or manually controlled or implemented by the user by manipulating a portion of the cryotherapy device 130.

[0048] Returning to the reference Figure 1A, in some embodiments, system 100 may include or be communicatively coupled to an intraoperative monitoring component 170. The intraoperative monitoring component 170 is operatively coupled to and / or integrated with the control component 110. The intraoperative monitoring component 170 may acquire signals associated with a cryotherapy procedure before, during, and / or after the cryotherapy procedure. The intraoperative signals may indicate the status of the target site, the area around the target site, and / or parameters associated with the cryotherapy treatment. The monitoring component 170 may detect signals related to the parameters of tissue, nerve fibers, and / or other structures at or near the target site. For example, the monitoring component 170 may provide information indicating when the tissue and / or other structures are at or near a reparable injury to the tissue, when the tissue and / or other structures are near an irreparable injury at or near the target site, the thermal distribution at or near the target site, an image at or near the target site, the effect of cryotherapy on the nerves at the target site, the presence of a particular structure at or near the target site, and / or the propagation of a cold line at or near the target site. During cryotherapy, a refrigerant may be applied at or near the target site to modulate nerve fibers (e.g., sympathetic nerves) at or near the target site. Cryotherapy may include multiple refrigerant application cycles, with thawing occurring during the time interval between two consecutive refrigerant applications. The damage may be reparable or irreparable, depending on one or more factors, including, for example, the temperature of the refrigerant, the flow rate of the refrigerant, the duration of the period of applying the refrigerant at or near the target site, the duration of the interval between two consecutive refrigerant applications at or near the target site, etc., or a combination thereof. In some embodiments, an exemplary cooling cycle may have a duration of from 10 seconds to 480 seconds (e.g., 240 seconds). In other embodiments, the cycle time may be different.

[0049] In some embodiments, the intraoperative monitoring component 170 may be configured to transmit intraoperative signals to the control component 110 before, during, and / or after the cryotherapy procedure, such that the control component 110 may control refrigerant delivery based on the intraoperative signals. The intraoperative monitoring component 170 may transmit the detected information to a user (e.g., displayed on the display 112, displayed on the user's mobile device), and the user may provide user instructions to the control component 110, such that the control component 110 adjusts the procedure based on the user instructions. In some embodiments, these controls may be automated based on feedback signals.

[0050] In some embodiments, the intraoperative signals detected by the monitoring component 170 may include electrical signals, imaging data, physiological parameters, and / or operating parameters of a support device coupled to the subject during cryotherapy (e.g., the operation of a ventilation device). The information may be provided in real time and / or as a change between different time points.

[0051] The intraoperative monitoring component 170 can be operatively coupled to a monitoring device along the shaft 132, the handle 138, and / or the cooling assembly 140 to measure various parameters of the surrounding anatomical structure and the effectiveness of cryotherapy. The monitoring device can include, for example, temperature sensors (e.g., thermocouple sensors), oxygen meters, CO 2 meters, pressure sensors, electrodes, and / or imaging devices. In some embodiments, the monitoring device can be a device that is separate from the cryotherapy device 130 and delivered separately at or near the target site. In some embodiments, the monitoring component 170 can be a device that is external to and communicates with the control component 110, the display 112, and / or a user device (e.g., a mobile device, a tablet).

[0052] Targeted pulmonary denervation performed with the system 100 can denervate the bronchial branches of the vagus nerve to reduce hyperreactivity, thereby reducing airway constriction, inflammation, and / or mucus production. It is expected that targeted pulmonary denervation performed according to embodiments of the present technology will produce a therapeutic effect in patients with COPD, including, for example, reducing the occurrence or severity of exacerbations, altering the course of decline in pulmonary function tests (PFTs), and / or improving the quality of life of the patient.

[0053] The system 100 is configured to affect tissue at a depth beyond the tissue it contacts, so as to affect structures located away from the tissue in contact with the cooling assembly 140, such as nerves. This "ablation zone" applies thermal damage to nerve fibers located at a certain distance from the bronchial lumen. The distance from the bronchial lumen and the size of the ablation zone can depend at least in part on the duration of ablation and the number of ablation cycles. For example, the system 100 can ablate nerve fibers located 1 mm - 3 mm from the inner wall of the bronchial lumen. In some embodiments, the system 100 can apply thermal damage to nerve fibers more than 3 mm from the inner wall of the bronchial lumen. In some embodiments, the thermal damage can be acute, while in other embodiments, the damage occurs some time after the initial ablation surgery (e.g., 7 - 30 days later). In some embodiments, the thermal damage to certain portions of the affected area (e.g., selected tissue) heals after a period of time, while other portions (e.g., nerve fibers) can be completely ablated.

[0054] Figure 3 The airway anatomy with exemplary treatment positions for cryotherapy procedures according to some embodiments of the present technology is shown. The airway includes the trachea T that branches into the right main bronchus RMB and the left main bronchus LMB. The right main bronchus RMB further branches into smaller bronchi and bronchioles within the lung tissue of the right lung, including the right upper lobe bronchus RULB and the right intermediate bronchus RILB. The left main bronchus LMB further branches into smaller bronchi and bronchioles within the lung tissue of the left lung, including the left upper lobe bronchus LULB and the left lower lobe bronchus LLLB. As Figure 3As shown, the treatment sites 301 (individually identified as the first through seventh treatment sites 301a - g, respectively) can be positioned within the right main bronchus (RMB) and left main bronchus (LMB), and distal therefrom beyond the bifurcation, within the right and left upper lobe bronchi (RULB, LULB), the right intermediate bronchus (RILB), and the lower lobe bronchi (LLLB). Thus, the cryotherapy device disclosed herein, such as Figure 1A device 130, has a shaft and an end effector that are sized, shaped, and configured to navigate through the tortuous airway anatomy and into airways outside of the main right and main left bronchi, which have smaller diameters. For example, the angle between the axis of the right main bronchus (RMB) and the right upper lobe bronchus (RULB) (referred to as the right upper lobe bronchus angle θ) can be an obtuse angle that requires the shaft of the cryotherapy device (e.g., Figures 1A - 1C device 130) to navigate substantial curvature to reach any target site within the right upper lobe bronchus (RULB). Thus, in order to reach a treatment location in the airway that is distal from the bifurcation of the right main bronchus (RMB) and the right upper lobe bronchus (RULB), the shaft of the cryotherapy device 130 ( Figures 1A - 1C ) must be able to flex or otherwise bend at an angle that is substantially the same as or similar to the right upper lobe bronchus angle θ. The ability to treat the main bifurcation and distal to the bifurcation beyond the main right and main left bronchi allows the present technique to avoid important anatomical structures (e.g., blood vessels, nerves not relevant to this indication) to prevent the cryotherapy cooling from adversely affecting nearby structures.

[0055] As described above, the size, shape, and configuration of the cryotherapy device 130 can be designed to be used in conjunction with a bronchoscope to navigate and visualize a cryotherapy procedure directed to a treatment location. The positioning of the cryotherapy device 130 or a portion thereof can be visualized via the bronchoscope, thereby allowing the user to precisely navigate and position the catheter within the airway. This can allow for accurate targeting of specific areas within the airway that require treatment. Additionally, the bronchoscope can provide real - time visualization of the airway during the procedure, thereby allowing the user and / or the system to monitor the treatment site and make adjustments as needed to ensure effective treatment and minimize damage to surrounding tissue. Examples of adjustments include repositioning the cooling assembly 140, adjusting parameters of the refrigerant delivery (e.g., the pressure and / or flow rate of fresh refrigerant to or from the cryotherapy device 130, the injection direction of fresh refrigerant leaving the cryotherapy device 130 via the nozzle, the refrigerant flow duration, the time interval between freezing and thawing in an ablation cycle, etc., or combinations thereof).

[0056] Figure 4 Illustrated is the use of a cryotherapy catheter configured according to an embodiment of the present technique (e.g., Figures 1A - 1CBronchoscopic images of cryoablation procedures of a cryoablation device 130). The procedure can be initiated by first advancing a bronchoscope (e.g., Figure 1A bronchoscope 160) of ) into the treatment site within the bronchus (e.g., within the right or left branch, beyond the bifurcation of the right or left branch). Then the distal portion of the catheter can be inserted through the working channel of the bronchoscope and beyond the distal opening of the working channel such that it protrudes beyond the bronchoscope and can be visualized, as shown in step 405. Then, the inflatable member can optionally be inflated (e.g., with air or other gas) to confirm that the outer surface of the inflatable member provides proper juxtaposition against the tissue of the airway inner wall. Although a catheter with a semi-compliant balloon is designed to provide adequate juxtaposition and treat a wide range of diameters, if the inflatable member does not provide adequate juxtaposition, e.g., because it is too large or too small, the catheter can be removed and a balloon of a different size can be used. After confirming proper juxtaposition, the inflatable member can be deflated and optionally retracted into the bronchoscope to allow the bronchoscope to capture one or more images of the treatment site.

[0057] Once the clinician is ready to perform ablation, the catheter can be moved back to the target position and the position of the cooling assembly can be confirmed (e.g., via radiopaque markers, by observing images / videos via the bronchoscope, and / or other suitable position confirmation mechanisms). The bronchoscope can optionally be positioned in a bronchoscope holder such that it remains stationary during the procedure. As shown in step 410, the inflatable member can then be inflated such that it presses against the tissue at the target position and delivery of the refrigerant for cryoablation neuromodulation can be initiated. In some embodiments, the patient is required to hold their breath immediately before the balloon is inflated such that there is little or no movement at the target site, thereby maintaining the position of the inflatable member at the target site.

[0058] As shown in step 425, initiation of the ablation step (i.e., by delivering the refrigerant to the cooling assembly) can cause ice to form around the outside of the inflatable member. This freezes the inflatable member to the surrounding tissue and stabilizes the position of the inflatable member relative to the target site. In some embodiments, the cryoablation cooling provided by the systems disclosed herein can cause an ice ball to form around the entire circumference of the inflatable member and adjacent to the airway wall or a portion thereof. In the case where the balloon adheres or otherwise fixes to the target site, the patient can release his or her breath hold. Delivery of the cryoablation cooling can continue (e.g., with or without a breath hold) until the desired cryoablation cycle of refrigerant delivery has been run. After completion of the cryoablation cooling, the procedure can be continued by deflating the balloon and capturing images (step 430) of the treatment site and / or taking measurements of the treatment site.

[0059] In some embodiments, cryotherapy cooling procedures may be performed multiple times at the same target site (e.g., balloon deflation, followed by reinflation for a second ablation cycle). In some embodiments, the cryotherapy device provides partial circumferential ablation, and thus the catheter may be rotated to ablate other portions along the circumference of the airway.

[0060] Combining a cryotherapy catheter with a bronchoscope can result in a less invasive procedure compared to traditional surgical methods, which can lead to reduced trauma to the treatment site and / or surrounding tissues, shorter recovery times, less pain, and minimized risk of complications. The flexible nature of both the bronchoscope and the catheter can allow access to remote or difficult-to-reach areas of the airway, which is common when treating conditions in the bronchi and other branches of the airway. See, for example, the treatment location at any of the positions shown as Figure 3 shown.

[0061] In addition to delivering cryotherapy cooling, the catheter can be configured for one or more various other purposes, including, for example, delivering drugs (e.g., analgesics, local anesthetics), fluids, and / or therapies directly to the target site, aspirating mucus or debris, detecting data around the target site, thereby allowing for customized treatment based on the patient's condition and needs.

[0062] Figure 5 A block diagram of a processing device configured to perform the control of system 100 in accordance with some embodiments of the present technology is shown. Processing device 500 may constitute an example of control component 110 ( Figure 1A ). Processing device 500 may be operatively coupled to console 102, display 112, input device, intraoperative monitoring component 170, and / or other devices or components of system 100 shown as Figure 1A or integrated therewith. Processing device 500 may be configured to receive information, data, signals, and / or other feedback, and generate control signals to control the operation of Figure 1A system 100 and its components.

[0063] Processing device 500 may include a memory 505 and a processor 510. Memory 505 may have instructions stored thereon. The instructions, when executed by processor 510, may configure processing device 500 (e.g., various modules or components of processing device 500) to perform the operations described elsewhere in this document, including, for example, those operations shown as Figure 7 . One or more processors 510 may include at least one processor and / or control circuitry to send and receive commands, requests, and other suitable data using one or more input / output (I / O) paths.

[0064] The control circuit may include any suitable processing, storage, and / or I / O circuitry. The processing device 500 may also include or be operatively connected to a user input interface and / or a user output interface. As referred to herein, a "user interface" may include human-machine interaction and communication in a device and may include a display screen for receiving and displaying data, input devices (e.g., keyboard, touch screen, mouse), and the appearance of a desktop. For example, the user interface may include the manner in which a user interacts with the control component and / or the intraoperative monitoring component.

[0065] In some embodiments, the processing device 500 may include a transmitter 515 and a receiver 520 that are respectively configured to send and receive information. At least one of the transmitter 515 or the receiver 520 may facilitate communication via a wired connection and / or a wireless connection between the processing device 500 and a device or information resource external to the processing device 500. For example, the processing device 500 may receive sensor data acquired by a sensor of the intraoperative monitoring component via the receiver 520. As another example, the processing device 400 may receive input from a user via the receiver 520. As another example, the processing device 500 may transmit a notification to a user (e.g., a medical professional, a display) via the transmitter 515. In some embodiments, the transmitter 515 and the receiver 520 may be integrated into one communication device.

[0066] Figure 6A and Figure 6B A side view of various refrigerant delivery assemblies in accordance with some embodiments of the present technology is shown. As Figure 6A shown, the refrigerant delivery assembly 600A includes a balloon 620A and a separate lumen 660 that is in fluid communication with a patient's airway. When the refrigerant delivery assembly 600A is in place and the balloon 620A is in an inflated configuration, the lumen 660 may allow for lung ventilation, mucus clearance, or positioning of a device (e.g., a guide wire, a mucus clearance device), etc., or a combination thereof. The refrigerant delivery assembly 600A may include an injection tube attached to an outer wall of the lumen 660 opposite the balloon 620A.

[0067] As Figure 6B shown, the refrigerant delivery assembly of the catheter 600B includes a balloon 620B attached to the distal end of an elongate shaft 610 and an injection tube 630B that at least partially extends beyond the elongate shaft 610. The catheter 600B may include a delivery line 670 through which fresh refrigerant is delivered from a cryogenic console (e.g., the console 102 shown in FIG. 1) to a target site or near the target site. The injection tube 630B may be in fluid communication with the distal end of the delivery line 670 or be the distal end of the delivery line 670. The delivery line 670 may be similar to as Figure 1AThe delivery line 106 shown in [figure reference] has the delivery line 670 positioned on the outer wall of the elongate shaft 610 and helical along the outer wall of the elongate shaft 610 and straightening near (e.g., just proximal to) the location where the balloon 620B is attached to the elongate shaft 610. Benefits of this exemplary configuration of the delivery line 670 can include one or more of the following: helping to maintain temperature stability of the refrigerant and stabilizing the ablation cycle due to the temperature stability, allowing distal flexibility; increasing the compressive strength, torque, and / or pushability of the catheter 600B, and / or facilitating twisting of the balloon 620B when the balloon 620B is packed for delivery (towards or away from a target site in the airway).

[0068] Figure 7 is a flow chart showing a cryotherapy procedure 700 according to some embodiments of the present technology. At 710, a cooling assembly of a cryotherapy device of a cryotherapy system can be placed at or near a target site of an object (e.g., a patient). The target site can be a treatment location in the airway of the object. The treatment location can be a location along the airway away from a bifurcation such that the air passage downstream of the treatment location can be modified. Exemplary treatment locations can include locations at the right upper lobe bronchus, right middle bronchus, left upper lobe bronchus, and left lower lobe bronchus.

[0069] The cooling assembly can be part of a catheter sized to fit within the lumen of a bronchoscope or otherwise attached to the bronchoscope (e.g., attached to the outside of the bronchoscope) such that the refrigerant delivery assembly can be delivered to a target site or near a target site in the airway by inserting the lumen of the bronchoscope into the airway. The positioning of the refrigerant delivery assembly can be observed or verified based on the view provided by the bronchoscope and / or feedback from a monitoring component of the cryotherapy system.

[0070] The cooling assembly can include an expandable member, such as a balloon, and an injection tube configured to deliver a refrigerant to the balloon. The balloon can move from a first or deflated configuration to a second or inflated configuration (by delivering a gas or other fluid into the balloon) such that the inflated balloon is juxtaposed with the adjacent airway wall at the target site. The refrigerant is discharged through an opening of the injection tube into the balloon to provide cryotherapy cooling. The balloon can be configured to facilitate heat transfer between the tissue under the inner wall of the body cavity and the refrigerant in the balloon, where the balloon contacts the inner wall such that at least a portion of the tissue undergoes cryoablation during the cryotherapy procedure 700.

[0071] In 720, at least one of intraoperative signals or user instructions can be received at a console of a cryotherapy system. The user instructions can be responsive to the intraoperative signals. The intraoperative signals can be obtained while treating a subject in a cryotherapy procedure 700 guided to a target site as described in 710. The intraoperative signals can indicate a status at or near the target site. The status (including its changes) can be caused by the cryotherapy procedure 700 and can thus be used to control the progress of the cryotherapy procedure by controlling refrigerant delivery.

[0072] In 730, the console can control a refrigerant delivery assembly to deliver refrigerant to or near the target site based on at least one of the intraoperative signals or user instructions. For example, the console can cause the refrigerant delivery assembly to maintain the delivery of refrigerant to or near the target site, pause the delivery of refrigerant to or near the target site; resume the delivery of refrigerant to or near the target site; or move at least a portion of the refrigerant delivery assembly away from the target location. By way of example only, the console can automatically divert or stop the refrigerant flow after a set time, using an electronic or mechanical timer to manage a valve operatively connected to the cryo console. Alternatively, the timer can be built into the catheter, possibly within its handle.

[0073] Some aspects of the present disclosure include a kit for a cryotherapy procedure in accordance with some embodiments of the present technology. The components for practicing the methods of the present technology can be packaged and provided to a medical professional in the form of a kit. The kit can include a catheter having a delivery line, a balloon, and an injection tube, and a device for connecting the catheter to a cryo console. By way of example only, the connecting device can include a luer connection at an end of the catheter opposite the injection tube. The connecting device can allow a user to conveniently connect the catheter to the cryo console to form a sealed fluid communication between the catheter and the cryo console such that the catheter can receive fresh refrigerant and deliver it to or near a target site within a patient's body and direct refrigerant emissions away from the target site. The catheter can be sized to fit within the lumen of a bronchoscope or attached to the outside of a bronchoscope such that the catheter can be delivered to or near a target site by inserting the bronchoscope. The kit can also include user instructions on how to use the catheter, including how to connect the catheter to the bronchoscope and / or the cryo console, applicable values or ranges of values for one or more operating parameters (e.g., pressure, flow rate, temperature of the refrigerant, etc. or combinations thereof suitable for the catheter), compatible bronchoscopes and / or cryo consoles with which the catheter can be used. The kit can be sealed in a sterile manner for opening during a procedure.

[0074] Alternative embodiments of monitoring systems and methods

[0075] As described above, the cryotherapy system disclosed herein can be configured to detect signals (referred to as "intraoperative signals") from various devices (e.g., sensors) associated with the system disclosed herein, which can include electrical signals, imaging data, physiological parameters, and / or operating parameters of support devices coupled to the subject during cryotherapy (e.g., operation of a ventilation device), and this information can be provided in real time and / or as changes between different time points.

[0076] An intraoperative monitoring system (e.g., Figure 1A monitoring component 170) can include one or more monitoring components carried by the cryotherapy device, the bronchoscope, and / or other components of the cryotherapy system, and can be delivered into the body before, during, and / or after cryotherapy to measure various parameters of the surrounding anatomical structure and the effect of cryotherapy. The monitoring components can include temperature sensors (e.g., thermocouples), oxygen meters, CO 2 meters, pressure sensors, electrodes, and / or imaging devices. In some embodiments, the monitoring components can be separate devices delivered alone or to the surrounding anatomical structure (e.g., surrounding blood vessels) at or near the target site.

[0077] When the monitoring system includes a temperature sensor (e.g., thermocouple), the temperature sensor can measure the temperature at or near the target site (e.g., in the airway, tissue of the airway, tissue of the esophagus, surrounding blood vessels, and / or other structures) for a period of time before, during, and / or after the application of cryotherapy. The thermal distribution at or near the target site can be determined based on the measured temperature. For example, if the correlation between different thermal curves and corresponding cell / tissue damage in the subject is known, the state (including state changes) at or near the target site of the subject can be determined or estimated.

[0078] When the monitoring system includes an oxygen meter, the oxygen meter can measure the oxygen level in the air at or near the target site located in the airway. CO 2 meter can measure the CO 2 level in the air at or near the target site located in the airway. The oxygen level and / or CO 2 level or its change can be related to the metabolism at or near the target site, and thus indicate the state (e.g., cell / tissue damage caused by cryotherapy) at or near the target site. Therefore, based on intraoperative signals including temperature, oxygen level, and / or CO 2 level at or near the target site over time, the control component 110 can control the refrigerant delivery of the cooling component 140.

[0079] When the monitoring system includes a pressure sensor, the pressure sensor can measure the pressure at one or more points at or near the target site. For example, during cryotherapy, the pressure at each of two different points at or near the target site can be monitored over time, and the pressure difference that changes over time can be determined based on the pressure at each of the two different points that changes over time; the change in the pressure difference over time can indicate the state of the target site or its vicinity. As another example, considering that the airway is usually close to the corresponding artery, the arterial pressure can be monitored as an approximation of the pressure at or near the target site in the airway. Based on the intraoperative signal including the pressure at each of the two different points and / or the pressure difference over time between the two different points, a control component (e.g., Figure 1A the control component 110) can control the delivery of the refrigerant to the cryotherapy device.

[0080] In some embodiments, the monitoring component includes one or more electrodes (e.g., an electrode pair) for measuring electricity at or near the target site. The electrical signal can include, for example, the resistance or impedance of a part of an object at or near the target site, which indicates the conductivity or its change or is related thereto of that part of the object. The change in conductivity can be due to changes in cell / tissue composition and / or metabolism caused by, for example, cell / tissue damage, indicating the state (including state changes) at or near the target site. Based on the intraoperative signal including the electrical signal that changes over time, the control component can control the delivery of the refrigerant to the cryotherapy device.

[0081] In some embodiments, the intraoperative signal can be used to provide image data that provides a representation of the cold / frozen line and / or a representation of the frozen cells / tissue (e.g., appearing as a cryogenic ice ball in the image). The cold / frozen line can be the interface between the frozen cells / tissue and the normal or unfrozen cells or tissue. The imaging device can include an ultrasound device, a fluoroscope, a computed tomography (CT) scanner, a tomosynthesis scanner, etc. In some embodiments, the imaging device can be portable so that it can be moved to the operating room to perform intraoperative monitoring.

[0082] In various embodiments, the monitoring assembly as disclosed herein can be used to detect physiological parameters to select the target site, determine the condition during cryotherapy, and / or determine the effectiveness of cryotherapy. An anesthesia plan can be set to allow spontaneous breathing before, during, and / or after the ablation procedure to monitor the physiological parameters or their changes intraoperatively before and after the ablation procedure. Such physiological parameters or their changes can be used as intraoperative signals for guiding the ablation procedure. Examples of the physiological parameters or their changes to be monitored can include changes in the CO 2 level in the airway near the target site before, after, and / or during the ablation procedure (e.g., CO 2Cumulative values), changes in respiratory rate, changes in respiratory sinus arrhythmia, changes in metabolic activity (metabolic tracking / monitoring, where one or more metabolic parameters are tracked or monitored), arterial pressure in an artery near a target site in the airway, cardiac plexus activity, changes in the oxygenation requirements of anesthesia.

[0083] In various embodiments, a monitoring assembly as disclosed herein may employ an electromyogram (EMG) catheter or another metal frame having one or more sensors. Figure 8 Various EMG catheters having EMG sensors 8080 (e.g., metal frames) are shown, the EMG sensors 8080 being positioned in veins and arteries around a target site within the bronchus before, during, and / or after a cryotherapy procedure, the target site being near the location of the cryotherapy end effector 8082 (e.g., Figures 1A - 1C of the cooling assembly 140). The electrical signals obtained using the EMG sensors 8080 can be used as signals before, after, and / or during an ablation procedure to guide the performance of the ablation procedure and / or determine efficacy. The EMG sensors 8080 can be metal frames configured to expand to attach to the inner wall of the lumen in which they are located (e.g., within a vein or artery). The EMG sensors 8080 can be placed in adjacent veins or arteries located adjacent to a target site in the airway. For example, considering that metal elements can generate signals for echolocation using the EMG sensors 8080, or the relative positioning of the cryotherapy end effector and surrounding anatomy can be confirmed on fluoroscopy, the electrical resistance in adjacent pulmonary veins or arteries can be monitored at a specified distance from the catheter. The EMG sensors 8080 can be maintained in place during an ablation procedure, and a modification of the EMG signal during an ablation procedure can be due to the formation and propagation of freezing, which in turn can indicate that a specific ablation depth has been achieved. In various embodiments, a mapping catheter can be used in a similar adjacent location to seek electrical signals (resistance, impedance) before, during, and / or after an ablation procedure, since the electrical conduction properties can change due to freezing and cellular injury / edema after an ablation procedure treatment.

[0084] In various embodiments, a monitoring system can include an ECG catheter in the stomach or esophagus, which can be used for intraoperative monitoring of esophageal plexus or main vagus nerve activity. The electrical signals obtained using the ECG catheter can be used as intraoperative signals to guide the performance of an ablation procedure. For example, if a modification to the esophageal ECG signal is identified, the ablation procedure can be immediately stopped.

[0085] In various embodiments, the monitoring system may include a detection component for phrenic nerve monitoring and may perform intraoperative monitoring by pacing the main vagus nerve activity to highlight pulmonary nerve activity, thereby better amplifying the differences in pulmonary nerve activity during and after the ablation process. The electrical signals corresponding to the pulmonary nerve activity may be used as intraoperative signals to guide the ablation procedure.

[0086] In various embodiments, the monitoring system may include a component that provides real-time imaging, such as a CT scanner, to monitor the freezing of cells and / or tissues at or near the target site of the subject. The imaging data thus obtained using the imaging device may be used as an intraoperative signal to guide the ablation process. For example, using real-time CT imaging, the frozen cells and / or tissues may appear as ice masses (e.g., ice balls) that gradually change (e.g., grow) in the CT images thus obtained.

[0087] In various embodiments, the monitoring system may include a component that detects and / or receives information related to mechanical ventilation parameters. Changes in mechanical ventilation during the ablation process and changes in the respiratory rate of the subject being treated in the ablation process may be monitored intraoperatively to guide the ablation process. The operating parameters of the support device (e.g., ventilation device), the respiratory rate of the subject, etc. or a combination thereof may be used as intraoperative signals to guide the ablation procedure.

[0088] Embodiments

[0089] The following embodiments illustrate several implementation manners of the present technology.

[0090] 1. A catheter, comprising:

[0091] An elongate shaft configured to accommodate a delivery line and a discharge lumen, wherein:

[0092] The delivery line is configured to receive a refrigerant and deliver the refrigerant to a target site in or near the airway, and

[0093] The surgical discharge lumen is configured to direct the refrigerant discharge away from the surgical target site,

[0094] A balloon connected to the distal end of the elongate shaft, and

[0095] An injection tube in fluid communication with the delivery line and configured to inject the refrigerant into the balloon, allowing the refrigerant to be in thermal communication with the target site through the injection tube, wherein,

[0096] The surgical catheter is sized to fit within the lumen of a bronchoscope such that at least a portion of the surgical balloon or the surgical injection tube is configured to be delivered to the surgical target site or near the surgical target site by inserting the lumen of the bronchoscope into the surgical airway.

[0097] 2. The catheter according to Example 1, wherein:

[0098] The balloon has a deflated configuration and an inflated configuration,

[0099] When the balloon is being delivered towards the target site or retracted from the target site, the balloon is in the deflated configuration, and

[0100] The balloon is configured to be juxtaposed with the inner wall of the airway in the inflated configuration.

[0101] 3. The catheter according to Example 2, wherein the balloon is configured to at least partially occlude the portion of the airway where the balloon is juxtaposed with the inner wall when the balloon is in the inflated configuration.

[0102] 4. The catheter according to Example 2, wherein the balloon is configured to completely occlude the portion of the airway where the balloon is juxtaposed with the inner wall when the balloon is in the inflated configuration.

[0103] 5. The catheter according to Example 2, wherein:

[0104] The balloon is configured to at least partially retract into the elongate shaft when the balloon is in the deflated configuration, and

[0105] When the balloon is in the inflated configuration, at least partially extend beyond the elongate shaft.

[0106] 6. The catheter according to any one of the preceding examples, wherein:

[0107] The injection tube is configured to at least partially retract into the elongate shaft when the injection tube is being delivered towards the target site or retracted from the target site, and

[0108] The injection tube is configured to at least partially extend beyond the distal end of the elongate shaft when injecting a refrigerant into the balloon.

[0109] 7. The catheter according to any one of the preceding examples, wherein the injection tube has a plurality of openings through which the refrigerant is injected into the balloon.

[0110] 8. The catheter according to Example 7, wherein at least one of the plurality of openings includes a nozzle or an orifice through which the refrigerant undergoes expansion and pressure drop when being injected into the balloon.

[0111] 9. The catheter according to any one of the preceding examples, wherein the delivery line is located within the discharge lumen.

[0112] 10. A system for delivering a refrigerant, the system comprising:

[0113] A catheter, the catheter comprising:

[0114] A slender shaft configured to accommodate a delivery line and a discharge lumen, wherein:

[0115] The delivery line is configured to receive refrigerant and deliver the refrigerant to or near a target site in an airway, and

[0116] The discharge lumen is configured to direct the discharge of the refrigerant away from the target site,

[0117] A balloon connected to the distal end of the slender shaft, and

[0118] An injection tube in fluid communication with the delivery line and configured to inject the refrigerant into the balloon, allowing the refrigerant to be in thermal communication with the target site through the injection tube, wherein,

[0119] The catheter is sized to fit within the lumen of a bronchoscope such that the balloon and the injection tube are configured to be delivered to or near the target site by inserting the lumen of the bronchoscope into the airway.

[0120] 11. The system according to example 10, further comprising a bronchoscope configured to provide real-time visualization of at least a portion of the catheter as the catheter moves within the airway together with the bronchoscope.

[0121] 12. A kit for delivering refrigerant, the kit comprising a catheter as described in any one of examples 1-9.

[0122] 13. The kit according to example 12, further comprising instructions for using the catheter in cryotherapy.

[0123] 14. A method for delivering refrigerant, comprising:

[0124] Placing the refrigerant delivery assembly of a catheter as described in any one of examples 1-9 at or near a target site of an object;

[0125] Receiving at least one of an intraoperative signal or a user instruction in response to an intraoperative signal at a console of a cryotherapy system; and

[0126] Based on at least one of the intraoperative signal or the user instruction, controlling the refrigerant delivery assembly to deliver the refrigerant to the target site or near it.

[0127] Conclusion

[0128] The foregoing embodiments depict different components included within or connected to different other components. It should be understood that the architectures so depicted are merely exemplary, and that in fact many other architectures can be implemented that achieve the same functionality. In a conceptual sense, any arrangement of components that achieve the same functionality is effectively “associated” such that the desired functionality is achieved. Thus, any two components that are combined herein to achieve a particular functionality can be regarded as “associated” with each other such that the desired functionality is achieved, regardless of the architecture or intervening components. Similarly, any two components so associated can also be regarded as “operably connected” or “operably coupled” with each other to achieve the desired functionality.

[0129] While particular embodiments of the present technology have been shown and described, it will be apparent to those skilled in the art that, based on the teachings herein, changes and modifications can be made without departing from the technology and its broader aspects, and thus, the appended claims will encompass all such changes and modifications that are within the true spirit and scope of the technology. Additionally, it should be understood that the technology is defined only by the appended claims. Those skilled in the art will understand that, in general, the terms used herein, particularly the terms used in the appended claims (e.g., the body of the appended claims), are generally intended to be “open” terms (e.g., the term “comprising” should be interpreted as “including but not limited to,” the term “having” should be interpreted as “at least having,” the term “including” should be interpreted as “including but not limited to,” etc.). Those skilled in the art will further understand that if an intent to introduce a specific number of claim recitations is present, such intent will be explicitly recited in the claims, and in the absence of such recitation, no such intent exists. For example, for purposes of illustration, the following appended claims may contain the use of introductory phrases “at least one” and “one or more” to introduce claim recitations. However, the use of these phrases should not be construed as implying that the introduction of a claim recitation by the indefinite article “a” or “an” limits any particular claim containing such introduced claim recitation to a technology that includes only one such recitation, even when the same claim includes the introductory phrases “one or more” or “at least one” as well as the indefinite article “a” or “an” (e.g., “a” and / or “an” should generally be interpreted to mean “at least one” or “one or more”); the same holds true for the use of a definite article to introduce a claim statement. Additionally, even if a specific number of introduced claim recitations are explicitly recited, those skilled in the art will recognize that such recitations generally should be interpreted to mean at least the recited number (e.g., the bare recitation of “two recitations” without further modifiers generally means at least two recitations, or two or more recitations).

[0130] Unless otherwise expressly stated or otherwise clearly contradicted by the context, conjunctive language such as "at least one of A, B, and C" or a phrase in the form of "at least one of A, B, and C" (i.e., the same phrase with or without an Oxford comma) is understood in context to generally mean that an item, term, etc. can be A or B or C, any non-empty subset of the set A and B and C, or any set that includes at least one of A, at least one of B, or at least one of C that is not contradicted by or otherwise excluded from the context. For example, in an illustrative example of a set with three members, the conjunctive phrases "at least one of A, B, and C" and "at least one of A, B, and C" refer to any one of the following sets: {A}, {B}, {C}, {A, B}, {A, C}, {B, C}, {A, B, C}, and, if not expressly stated or contradicted by the context, any set that has {A}, {B}, and / or {C} as subsets (e.g., a set with multiple "A"s). Thus, such conjunctive language is generally not intended to imply that certain embodiments require the presence of at least one of A, at least one of B, and at least one of C each. Similarly, phrases such as "at least one of A, B, or C" and "at least one of A, B, or C" refer to the same sets as "at least one of A, B, and C", and "at least one of A, B, and C" refers to any one of the following sets: {A}, {B}, {C}, {A, B}, {A, C}, {B, C}, {A, B, C}, unless a different meaning is expressly stated or clear from the context.

Claims

1. A catheter, comprising: a slender shaft configured to accommodate a delivery line and a discharge lumen, wherein: the delivery line is configured to receive refrigerant and deliver the refrigerant to a target site in or near the airway, and the discharge lumen is configured to direct refrigerant discharge away from the target site, a balloon connected to the distal end of the slender shaft, and an injection tube in fluid communication with the delivery line and configured to inject the refrigerant into the balloon, allowing the refrigerant to be in thermal communication with the target site through the injection tube, wherein, the catheter is sized to fit within the lumen of a bronchoscope such that at least a portion of the balloon or the injection tube is configured to be delivered to the target site or near the target site by inserting the lumen of the bronchoscope into the airway.

2. The catheter according to claim 1, wherein: the balloon has a deflated configuration and an inflated configuration, the balloon is in the deflated configuration when being delivered towards the target site or retracted from the target site, and the balloon is configured to be juxtaposed against the inner wall of the airway in the inflated configuration.

3. The catheter according to claim 2, wherein, the balloon is configured to partially occlude the portion of the airway where the balloon is juxtaposed against the inner wall when the balloon is in the inflated configuration.

4. The catheter according to claim 2, wherein, the balloon is configured to completely occlude the portion of the airway where the balloon is juxtaposed against the inner wall when the balloon is in the inflated configuration.

5. The catheter according to claim 2, wherein: the balloon is configured to at least partially retract into the slender shaft when the balloon is in the deflated configuration, and at least partially extend beyond the slender shaft when the balloon is in the inflated configuration.

6. The catheter according to claim 1, wherein: the injection tube is configured to at least partially retract into the slender shaft when the injection tube is being delivered towards the target site or retracted from the target site, and the injection tube is configured to at least partially extend beyond the distal end of the slender shaft when injecting refrigerant into the balloon.

7. The catheter according to claim 1, wherein the injection tube has a plurality of openings through which the refrigerant is injected into the balloon.

8. The catheter according to claim 7, wherein at least one of the plurality of openings includes a nozzle or an orifice through which the refrigerant undergoes expansion and pressure drop when injected into the balloon.

9. The catheter according to claim 1, wherein, the delivery line is located within the discharge cavity.

10. A system for delivering refrigerant, the system comprising: a catheter, the catheter comprising: a slender shaft configured to accommodate a delivery line and a discharge lumen, wherein: the delivery line is configured to receive refrigerant and deliver the refrigerant to a target site in or near the airway, and the discharge lumen is configured to direct refrigerant discharge away from the target site, a balloon, the balloon being connected to the distal end of the elongate shaft, and an injection tube, the injection tube being in fluid communication with the delivery line and configured to inject the refrigerant into the balloon, allowing the refrigerant to be in thermal communication with the target site through the injection tube, wherein, the catheter is sized to fit within the lumen of a bronchoscope such that the balloon and the injection tube are configured to be delivered to the target site or near the target site by inserting the lumen of the bronchoscope into the airway.

11. The system according to claim 10, further comprising the bronchoscope, the bronchoscope being configured to provide real-time visualization of at least a portion of the catheter as the catheter and the bronchoscope are moved within the airway together.

12. A kit for delivering a refrigerant, the kit comprising a catheter according to any one of claims 1-9.

13. The kit according to claim 12, further comprising instructions for using the catheter in a cryotherapy procedure.

14. A method for delivering a refrigerant, comprising: placing the refrigerant delivery assembly of a catheter according to any one of claims 1-9 at or near a target site of an object; receiving at least one of an intraoperative signal or a user instruction in response to an intraoperative signal at a console of a cryotherapy system; and controlling the refrigerant delivery assembly to deliver the refrigerant to the target site or near the target site based on at least one of the intraoperative signal or the user instruction.

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