Patent Application
20240130775
The present technology relates generally to targeted neuromodulation in the lung. Several embodiments are directed to cryotherapeutic devices, systems, and methods for targeted lung neuromodulation.
Pulmonary diseases are characterized as pathologies that adversely affect performance of the lungs, making it difficult for air-breathing animals (e.g., humans) to perform the gas exchange necessary for survival. Certain pulmonary diseases, such as chronic obstructive pulmonary disease (“COPD”), asthma, and bronchiectasis, specifically affect the airways that carry oxygen into the body. For example, COPD and asthma are characterized by a narrowing or blockage of airways which can be the result of the thickening of airway walls, alterations in the structures within or around the airway walls, or combinations thereof. For example, blockages of airway lumens can be caused by excessive intraluminal mucus and/or edema fluid. Airway wall thickening can result from inflammation, contraction or hypertrophy of the airway smooth muscle, mucous gland hypertrophy, and/or edema. Structural changes around the airway can reduce radial traction on the airway wall and lead to a narrowing of the airway. This narrowing or obstruction of airways can significantly decrease the amount of gas exchanged in the lungs resulting in breathlessness.
COPD is characterized by airflow limitation and long-term respiratory symptoms, such as shortness of breath and cough. The two most common types of COPD are emphysema and chronic bronchitis. Emphysema is defined as enlarged airspaces (alveoli) with broken down walls resulting in permanent damage to the lung tissue. Chronic bronchitis is defined as a productive cough (i.e., producing mucus or phlegm) for at least three months for two years.
Cryotherapeutic systems and methods for targeted lung neuromodulation are disclosed herein. In some embodiments, for example, a cryotherapeutic system can include a cooling assembly (also referred to as an “end effector”) at a distal portion of a shaft for performing a cryotherapy procedure at one or more target sites within airways of a lung to modulate nerves (e.g., ablate, dennervate) for the treatment of COPD and/or other pulmonary diseases. In various embodiments, the cooling assembly can include an expandable member that receives refrigerant in a manner suitable for delivering cryotherapeutic 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 exhaust of refrigerant from the cooling assembly is based on one or more intraprocedural signals associated with feedback from the cryotherapy system. The intraprocedural signal(s) can provide feedback on various parameters at or surrounding the target site (also referred to as a treatment location) such that the cryotherapy can be performed in response to the provided parameters. In some embodiments, the cryotherapeutic device may be configured for use with a bronchoscope in a cryotherapy procedure such that a user (e.g., a physician performing the procedure) may visualize the target site before, during, and/or after the procedure.
Existing treatments of a pulmonary disorder include use of systemic or inhaled medication, e.g., corticosteroids, antibiotics, bronchodilators, aerosol delivery of a “mucolytic” agent (e.g., water, hypertonic saline solution). Many of these medications have serious side effects. A thermal ablation treatment, such as bronchial thermoplasty, another treatment option, involves destroying smooth muscle tone by ablating the airway wall in bronchial branches within a lung, thereby eliminating both smooth muscles and nerves in the airway walls of the lung. The treated airways may be unable to respond to inhaled irritants, systemic hormones, and both local and central nervous system input. Accordingly, this destruction of smooth muscle tone and nerves in the airway wall may therefore adversely affect lung performance. The present technology has been shown to cryogenically ablate neural fibers for the treatment of COPD and/or other respiratory diseases, while preserving smooth muscle tone and avoiding the systemic effects of medications.
Specific details of several embodiments of the technology are described below with reference to
With regard to the terms “distal” and “proximal” within this description, unless otherwise specified, the terms can reference a relative position of the portions of a cryotherapeutic device and/or an associated delivery device with reference to an operator and/or a location in the bronchus. For example, proximal can refer to a position closer to the operator of the device or an associated access point (e.g., the mouth), and distal can refer to a position that is more distant from the operator of the device or further from the access point.
Bronchial neuromodulation is the partial or complete incapacitation or other effective disruption of nerves innervating portions of the bronchi. In particular, bronchial neuromodulation includes inhibiting, reducing, and/or blocking neural communication along neural fibers (i.e., efferent and/or afferent nerve fibers) innervating the select bronchi. Such incapacitation can be long-term (e.g., permanent or for periods of months, years, or decades) or short-term (e.g., for periods of minutes, hours, days, or weeks). Bronchial neuromodulation is expected to efficaciously treat several clinical conditions characterized by increased activity of airway smooth muscle and mucus producing glands within the airways, such as COPD. The neuromodulation is expected to relax the airway smooth muscle, decrease mucus production, and/or decrease nervous system mediated inflammation and edema, which results in the reduction of airway obstruction and makes it easier to breathe.
As disclosed herein, cryotherapy can be used to partially or completely incapacitate neural pathways, such as those innervating the bronchi. Cryotherapy includes cooling tissue at a target site in a manner that modulates neural function. The mechanisms of cryotherapeutic tissue damage include, for example, direct cell injury (e.g., necrosis) and sublethal hypothermia with subsequent apoptosis. Exposure to cryotherapeutic cooling can cause acute cell death (e.g., immediately after exposure) and/or delayed cell death (e.g., during tissue thawing and subsequent hyperperfusion). Several embodiments of the present technology include cooling a structure at or near an inner surface of a wall of an airway such that proximate (e.g., adjacent) tissue is effectively cooled to a depth where nerves innervating the lungs reside (e.g., the phrenic nerves). For example, the cooling structure is cooled to the extent that it causes therapeutically effective, cryogenic neural modulation. Sufficiently cooling at least a portion of a nerve is expected to slow or potentially block conduction of neural signals to produce a prolonged or permanent reduction in neural activity.
Cryotherapy has certain characteristics that can be beneficial for intra airway neuromodulation. For example, rapidly cooling tissue provides an analgesic effect such that cryotherapies may be less painful than ablating tissue at high temperatures. Cryo therapies may thus require less analgesic medication to maintain patient comfort during a procedure compared to heat ablation procedures. Additionally, reducing pain mitigates patient movement and thereby increases operator success and reduces procedural complications. Cryotherapy also typically does not cause significant collagen tightening, and thus cryotherapy is not typically associated with airway stenosis.
Cryotherapies generally operate at temperatures that cause cryotherapeutic applicators to adhere to tissue. This can be beneficial because it promotes stable, consistent, and continued contact with the tissue along the inner wall of the bronchi during treatment. The typical conditions of treatment can make this an attractive feature because, for example, respiration causes the bronchi to rise and fall and thereby moves the target site, a patient can move during treatment, and/or a catheter associated with the cryotherapeutic applicator can move. Further, in procedures where a patient is asked to hold his/her breath to keep the target site stationary, the patient can exhale once the applicator is adhered to the target site. This reduces the duration of breath holding, which can often be difficult for those patients suffering from COPD or other pulmonary diseases the procedure is used to treat. Adhesion associated with cryotherapeutic cooling also can be advantageous when treating short bronchi in which stable intraluminal positioning can be more difficult to achieve.
Referring to
In some embodiments, the cryotherapeutic device 130 is configured to be used with a bronchoscope 160 that can be used to visualize the target site and aid in delivery of the cooling assembly 140 to the target site within the bronchus. For example, the distal portion of the bronchoscope 160 can be inserted into the nose or mouth of a subject (e.g., a human patient), and the distal portion 136 of the shaft 132 can be threaded through a working channel 162 of the bronchoscope 160 to navigate the cooling assembly 140 to a position 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 distal relative to a distal opening of the working channel 162 or retracting the bronchoscope 160, and the cooling assembly 140 can then deliver cryotherapeutic cooling to tissue at the target site. In such embodiments, the bronchoscope 160 can provide direct visualization to guide the cooling assembly 140 to one or more desired locations within the airways, as well as provide visualization during and/or after cryotherapeutic cooling. Suitable bronchoscopes 160 can include, but are not limited to, those manufactured by Olympus Corporation of the America of Center Valley, Pennsylvania.
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, refillable cylinder, or the like) that retains a sufficient volume of refrigerant to perform multiple cryotherapy procedures. The refrigerant housed within the supply component 104 may be liquid nitrogen, carbon dioxide, a hydrofluorocarb on (“HFC”; e.g., Freon®, R-410A, etc.), and/or other suitable compressed or condensed refrigerants that can be retained in the supply component 104 at a sufficiently high pressure to maintain the refrigerant in at least a substantially liquid state at ambient temperatures. the supply component 104 is configured to retain the refrigerant at a desired pressure. For example, in one embodiment, liquid N2O is contained in the supply container 104 at a pressure of 750 psi or greater so it is in at least a substantially liquid state at ambient temperatures. In other embodiments, the refrigerant can include. For example, when the refrigerant is liquid N2O, the supply component 104 can retain the refrigerant at a pressure of 750 psi (5,171.07 kPa) or greater to maintain the refrigerant in at least a substantially liquid state at ambient temperatures. In some embodiments, the supply component 104 can include one or more chambers (e.g., tanks, vessels) that receive the refrigerant exhaust (e.g., nitrogen gas) produced during cryotherapy. The supply component 104 can include features, such as one or more valves, configured to control the flow of the refrigerant from the supply component 104 to cooling assembly 140 at the distal portion 136 of the cryotherapeutic device 130. A flow sensor may be included in or coupled to the supply component 104, the supply line 106, and/or the exhaust line 108 for sensing or measuring refrigerant flow to and/or from the cryotherapeutic device 130. As shown in
As further shown in
In various embodiments, the control component 110 can also be configured to generate control signals that control the delivery of refrigerant from the supply component 104, control the operation of the cryotherapeutic device 130, and/or send/receive signals from the cryotherapeutic device 130 and/or other devices associated with the cryotherapeutic procedure (e.g., patient vitals, the 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 cryotherapeutic device 130 to initiate, maintain, adjust, pause, stop, and/or resume refrigerant delivery to a treatment location of the subject in response to user inputs and/or an intraprocedural signal (e.g., detected from a sensor associated with the system 100).
In the embodiment illustrated in
Referring now to
The elongated shaft 132, the delivery lumen 133, and/or the exhaust lumen 135 may be made of a material that is substantially inert to the refrigerant, substantially insert to and biocompatible with the physiological environment of the airway, and/or sufficiently flexible at or near the temperature of refrigerant exhaust. In some embodiment, for example, the elongated shaft 132 may be made of a multilayer braided thermoplastic elastomer material (e.g., thermoplastic polyurethanes, thermoplastic copolyester (e.g., PEBAX)) and can have an outer diameter of 0.09 inch (or 2.3 millimeters). The delivery lumen 133 and/or the injection tube 144 can 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 sufficiently flexible at or near the temperature of fresh refrigerant or refrigerant exhaust to be delivered to a target site in the airway while sustaining the pressure of the fresh refrigerant or the refrigerant exhaust and the pressure and/or temperature drop when fresh refrigerant is sprayed. For example, the injection tube 144 can be made of Nitinol. In various embodiments, the shaft 132 and/or the injection tube 144 can be made from other suitable materials and/or have different dimensions suitable for delivery to the target site.
The expandable member 142 can have two configurations: a delivery state and an expanded state (shown in
In the expanded state, the expandable member 142 is inflated (e.g., via a lumen in communication with the interior of the expandable member 142) or otherwise expanded to define an interior chamber suitable for receiving refrigerant. For example, the expandable member 142 can be positioned beyond the distal end of the bronchoscope 160 such that it is positioned at the target site and expanded to abut and/or press against adjacent tissue of the airways. When the fresh refrigerant is being delivered from the injection tube 144 into the expandable member 142 via, e.g., one or more openings 146 on the injection tube 144, the refrigerant undergoes rapid expansion due to the pressure drop, thereby transitioning from liquid to gas, and effectuating the rapid cooling of the surrounding tissue for cryotherapeutic neuromodulation. Refrigerant continues to be delivered to within the expandable member 142, and thus the already expanded refrigerant exhausts through the exhaust port 148 to be guided away from the target site via the exhaust lumen 135.
In the inflated configuration, the expandable member 142 can expand radially to conform to the shape of the airway so that the refrigerant can touch or in close proximity to the target site on the wall of the airway.
The expandable member 142 can be sized and shaped such that, when in the expanded state, the expandable member 142 can oppose the inner walls of the adjacent airway section to secure the expandable member 142 in place. For example, the expandable member 142 may be configured to appose the internal wall of the airway circumferentially at a cross section. Further, the expandable member 142 may be made from a compliant and/or semi-compliant material that allows the expandable member to fit within various different airway sizes while also conforming at least partially to an interior wall of an airway so as to press against or abut the tissue. For example, the expandable member 142 can be sized 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 adequately press against and treat airway lumens have a diameter of 12-15 mm, which is the typical size of the left lower lobe bronchus and the right intermediate lobe bronchus, and/or lumens as small as 9 mm (e.g., the typical size of the right upper lobe bronchial). In some embodiments, the expandable member can treat smaller or larger airway lumens. The expandable member 142 can also be made from a material that provides for and can withstand rapid heat transfer to allow for the cryotherapeutic cooling of adjacent and surrounding tissue. The material may be substantially inert to and biocompatible with the physiological environment of the airway, and/or sustain the temperature of the refrigerant expelled from the injection tube 144 at which cryotherapy proceeds. For example, the expandable member 142 may be made of polyurethane, polyethylene, polytetrafluoroethylene (PTFE), polyvinyl chloride (PVC), nylon, PEBAX, silicone, polyimide, polypropylene, or the like, or a combination thereof.
The one or more openings 146 along the injection tube 144 can be located in select positions along the length and/or circumference of the injection tube 144 to provide for a desired cryoablation pattern. For example, the openings 146 can be oriented in a manner that creates one or more fully circumferential lesions that are 360° at a cross section. This cryoablation pattern may be further enhanced by delivering the refrigerant from the injection tube 144 substantially uniformly in the circumferential direction along a desired cross section. This may be achieved by, for example, arranging openings 146 on the injection tube 144 substantially uniformly in the circumferential direction.
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 exhibit a non-occlusive cross section such that the cross-section of the expandable member 142 touches only a portion of a circumferential segment of the internal wall at any cross section of the airway. For example, the expandable member 142 may have non-occlusive and eccentric cross sections configured to form ablation of a linear shape, a curved shape, or a spiral shape, over a segment of the airway. The non-occlusive expandable member 142 may allow lung venting, clearing mucus, or positioning a device (e.g., a guidewire, a mucus clearing device), or the like, or a combination thereof, when the expandable member 142 is at the inflated configuration.
As further shown in
In some embodiments, the cooling assembly 140 can include one or more sensors 154 that detects one or more parameters within the cooling assembly 140. For example, the sensor 154 can be a thermocouple that measures the temperature within the expandable member 142. This information can be communicated to the console 102 (
In various embodiments, the cooling assembly 140 can further include a valve, e.g., a needle valve, a Joule-Thomson throttle, a throttle element, or the like, for providing a pressure drop and a lower downstream temperature, thereby alter and/or enhance the effect and/or efficiency of the cryotherapeutic ablation. For example, a Joule-Thomson throttle can recover work energy from the expansion of the refrigerant resulting in a lower downstream temperature.
As further shown in
As shown in
In some embodiments, the injection tube 144 may include an external tube and a delivery sheath where the refrigerant delivery holes 146 are located. The delivery sheath may extend beyond or retract into the injection tube 144. The number (or count) of the refrigerant delivery holes 146 operable to dispel refrigerant to the interior of the expandable member 142 may be adjusted by adjusting the length of the delivery sheath extending beyond the external tube of the injection tube 144. In some embodiments, the delivery sheath may be rotatable such that the direction at which the refrigerant is sprayed into the expandable member 142 may be adjusted by rotating the delivery sheath. The adjustment (e.g., rotation, extension, or retraction) of the delivery sheath may be controlled or implemented under the control of the handle 138 (
Referring back to
In some embodiments, the intraprocedural monitoring component 170 can be configured to transmit the intraprocedural signals to the control component 110 before, during, and/or after a cryotherapy procedure such that the control component 110 may control the refrigerant delivery based on the intraprocedural signals. The intraprocedural monitoring component 170 can transmit information based on the detected to a user (e.g., displayed on the display 112, displayed on a mobile device of the user), and the user may provide a user instruction to the control component 110 such that the control component 110 adjusts the procedure based on the user instruction. In some embodiments, these controls can be automated based on the feedback signals.
In some embodiments, the intraprocedural signals detected by the monitoring component 170 can include electrical signals, imaging data, physiological parameters, and/or an operation parameter of a support device (e.g., the operation of a ventilation device) that is coupled to the object during cryotherapy. The information can be provided in real time and/or provided as a change between different points in time.
The intraprocedural monitoring component 170 can be operable coupled to a monitoring device along the shaft 132, the handle 138, and/or the cooling assembly 140 to measure various parameters of the surround anatomy and the effects of the cryotherapy. The monitoring device can include, for example, a temperature sensor (e.g., a thermocouple sensor), an oxygen meter, a CO2 meter, a pressure sensor, an electrode, and/or an imaging device. In some embodiments, the monitoring device can be a device separate from the cryotherapeutic device 130 and delivered separately at or near the target site. In some embodiments, the monitoring component 170 can be a device external to and in communication with the control component 110, the display 112, and/or a user device (e.g., a mobile device, tablet).
Targeted lung denervation performed with the system 100 can denervate the bronchial branches of the vagal nerve to reduce hyperreactivity, thereby reducing airway constriction, inflammation, and/or mucus production. Targeted lung denervation performed according to embodiments of the technology is expected to produce a therapeutic effect in COPD patients including, e.g., reduced occurrence or severity of exacerbations, an altered course of decline in a Pulmonary Function Test (PFT), and/or improvement in the quality of life of a patient.
The system 100 is configured to affect tissue at a depth beyond the tissue which it contacts so as to affect structures, such as nerves, positioned a distance away from the tissue in contact with the cooling assembly 140. This “ablation zone,” imparts thermal injury to neural fibers a distance from the bronchial lumen. The distance from the bronchial lumen and size of the ablation zone can depend, at least in part, on the duration of ablation and the number of cycles of ablation. For example, the system 100 can ablate neural fibers positioned 1 mm-3 mm from the inner wall of a bronchial lumen. In some embodiments, the system 100 can impart thermal injury to neural fibers more than 3 mm from the inner wall of the bronchial lumen. In some embodiments, the thermal injury can be acute and in others the injury occurs a time period after the initial ablation procedure (e.g., 7-30 days after). In some embodiments, the thermal injury to certain portions of the affected region (e.g., select tissue) heal after a period of time, whereas other portions, such as neural fibers, can be completed ablated.
As discussed above, the cryotherapeutic device 130 may be sized, shaped, and configured for use with a bronchoscope to navigate and visualize a cryotherapy procedure directed at a treatment location. The positioning of the cryotherapeutic device 130, or a portion thereof, may be visualized via the bronchoscope, thereby allowing the user to precisely navigate and position the catheter within the airway. This may allow for accurate targeting of a specific area in the airway that needs treatment. In addition, the bronchoscope may 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 an adjustment if needed to ensure effective treatment and minimizing damage to surrounding tissues. Examples of adjustments include repositioning the cooling assembly 140, adjusting a parameter of the refrigerant delivery (e.g., the pressure and/or a flow rate of fresh refrigerant to the cryotherapeutic device 130 or refrigerant exhaust from the cryotherapeutic device 130, an injection direction of fresh refrigerant exiting the cryotherapeutic device 130 via a nozzle, refrigerant flow duration, a time interval between freezing and thawing in an ablation cycle, or the like, or a combination thereof).
Once the clinician is ready for the ablation, the catheter can be moved back to the target location and the position of the cooling assembly can be confirmed (e.g., via the radiopaque markers, by viewing images/video via the bronchoscope, and/or other suitable location 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 expandable member can then be inflated such that it presses against the tissue at the target location and the delivery of refrigerant for cryotherapeutic neuromodulation can be initiated. In some embodiments, the patient is asked to hold his or her breath immediately before balloon inflation such that there is little to no movement at the target site, thereby maintain the position of the expandable member at the target site.
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 exterior of the expandable member. This freezes the expandable member to the surrounding tissue and stabilizes the position of the expandable member relative to the target site. In some embodiments, the cryotherapeutic cooling provided by the systems disclosed herein can cause an ice ball to form around an entire circumference of the expandable member and the abutting airway wall, or a portion thereof. With the balloon adhered or otherwise secured at the target site, the patient can release his or her breath hold. The delivery of cryotherapeutic cooling can continue (e.g., with or without breath holds) until the desired cryotherapeutic cycle of refrigerant delivery has run. Upon completion of the cryotherapeutic cooling, the procedure can continue by deflating the balloon and capturing an image of the treatment site (step 430) and/or taking measurements of the treatment site.
In some embodiments, the cryotherapeutic cooling procedure can be performed multiple times at the same target site (e.g., the balloon deflated and then reinflated for a second ablation cycle). In some embodiments, the cryotherapeutic device provide for partial circumferential ablation, and therefore the catheter can be rotated to ablate other portions along the circumference of the airways.
Combining the cryotherapeutic catheter with the bronchoscope may result in a less invasive procedure compared to traditional surgical methods, which may lead to reduced trauma to the treatment site and/or the surrounding tissues, shorter recovery times, reduced pain, and minimized risk of complications. The flexible nature of both the bronchoscope and catheter may allow access to remote or hard-to-reach areas of the airway, which is common in treating conditions in the bronchi and other branches of the airway. See, e.g., a treatment location at any one of locations as illustrated in
In addition to delivering cryotherapeutic cooling, the catheter may be configured to serve one or more various other purposes including, e.g., delivery of pharmaceuticals (e.g., analgesics, local anesthesia medicines), fluids, and/or therapies directly to the target site, suction of mucus or debris, detection of data surrounding the target site, thereby allowing for tailored treatments based on the patient's condition and needs.
The processing device 500 may include memory 505 and processor(s) 510. The memory 505 may have instructions stored thereupon. The instructions, upon execution by the processor(s) 510, may configure the processing device 500 (e.g., the various modules or components of the processing device 500) to perform the operations described elsewhere in the present document including, e.g., those illustrated in
The control circuitry may include any suitable processing, storage, and/or I/O circuitry. The processing device 500 may also include or be operably connected to a user input interface and/or user output interface. As referred to herein, a “user interface” may include a human-computer interaction and communication in a device and may include display screens for use in receiving and displaying data, input devices (e.g., a keyboard, a touchscreen, a mouse), and the appearance of a desktop. For example, a user interface may include a way a user interacts with the control components and/or the intraprocedural monitoring components.
In some embodiments, the processing device 500 may include a transmitter 515 and a receiver 520 configured to send and receive information, respectively. 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 sensors of an intraprocedural monitoring component via the receiver 520. As another example, the processing device 400 may receive input from a user via the receiver 520. As a further 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.
The refrigerant delivery assembly of a catheter 600B as illustrated in
The cooling assembly may be part of a catheter sized to fit within a lumen of a bronchoscope or otherwise attached to the bronchoscope (e.g., attached to an external side of the bronchoscope) such that the refrigerant delivery assembly may be delivered to or near the 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 views provided by the bronchoscope and/or feedback from monitoring components of the cryotherapy system.
The cooling assembly may include an expandable member, such as a balloon, and an injection tube configured to deliver refrigerant into the balloon. The balloon may move from a first or deflated configuration to a second or inflated configuration (via delivery of a gas or other fluid into the balloon) such that the inflated balloon apposes the adjacent airway wall at the target site. Refrigerant is dispelled through openings of the injection tube into the balloon to provide cryotherapeutic cooling. The balloon may be configured to facilitate heat transfer between the tissue underneath the internal wall of the body lumen and the refrigerant in the balloon where the balloon contacts the internal wall such that at least a portion of the tissue undergoes cryoablation in the cryotherapy procedure 700.
In 720, at least one of an intraprocedural signal or a user instruction can be received at the control console of the cryotherapy system. The user instruction can be in response to the intraprocedural signal. The intraprocedural signal can be acquired while the object is being treated in the cryotherapy procedure 700 directed to the target site as described in 710. The intraprocedural signal can indicate a status of the target site, or a vicinity of the target site. The status (including a change thereof) can be caused by the cryotherapy procedure 700, and therefore, can be used to control the proceeding of the cryotherapy procedure by controlling the refrigerant delivery.
In 730, the control console can control, based on at least one of the intraprocedural signal or the user instruction, the refrigerant delivery assembly to deliver the refrigerant to or near the target site. For instance, the control console can cause the refrigerant delivery assembly to maintain the delivery of the refrigerant to or near the target site, pause the delivery of the refrigerant to or near the target site; resume the delivery of the refrigerant to or near the target site; or cause at least a portion of the refrigerant delivery assembly to move away from the target site. Merely by way of example, the control console may automatically divert or halt a refrigerant flow after a set time, using an electronic or mechanical timer to manage a valve operably connected to a cryoconsole. Alternatively, this timer may be built into the catheter, perhaps within its handle.
Some aspects of the present disclosure include a kit for use in a cryotherapy procedure in accordance with some embodiments of the technology. Components to practice the method of the present technology may be packaged and provided to medical professionals in the form of a kit. The kit may include a catheter, having a delivery line, a balloon, and an injection tube, as well as a means for connecting the catheter to a cryoconsole. Merely by way of example, the connection means may include a luer connection on the opposite end of the catheter from the injection tube. The connection means may allow a user to conveniently connect the catheter to the cryoconsole to form a sealed fluid communication between the catheter and the cryoconsole so that the catheter can receive and deliver fresh refrigerant to or near a target site in the body of a patient and guide refrigerant exhaust away from the target site. The catheter may be sized to be fit within a lumen or attached to an external side of a bronchoscope so that the catheter may be delivered to or near the target size by inserting the bronchoscope. The kit may also include user instructions advising how to use the catheter, including how to connect the catheter to a bronchoscope and/or a cryoconsole, applicable values or value ranges of one or more operational parameters (e.g., the pressure, the flow rate, the temperature of refrigerant, or the like, or a combination t hereof, that are suitable for the catheter), compatible bronchoscopes and/or cryoconsoles where the catheter may be used. The kit may be sealed in a sterile manner for opening at the stie of a procedure.
As discussed above, cryotherapeutic systems disclosed herein can be configured to detect signals (referred to as “intraprocedural signals) from various devices (e.g., sensors) associated with the systems disclosed herein. These signals can include electrical signals, imaging data, physiological parameters, and/or an operation parameter of a support device (e.g., the operation of a ventilation device) that is coupled to the object during cryotherapy. The information can be provided in real time and/or provided as a change between different point in time.
The intraprocedural monitoring system (e.g., the monitoring component 170 of
When the monitoring system includes a temperature sensor (e.g., a thermocouple), the temperature sensor can measure the temperature at or near the target site (e.g., in the airways, tissue of the airways, tissue of the esophagus, the surrounding blood vessels, and/or other structures) over a time period before, during, and/or after cryotherapy application. A thermal profile at or near the target site may be determined based on the measured temperature. For instance, if the correlation between different thermal profiles and corresponding cell/tissue damage in the object is known, the status (including a status change) at or near the target site of the object may be determined or estimated.
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. The CO2 meter can measure the CO2 level in the air at or near the target site located in the airway. An oxygen level and/or an CO2 level, or a change thereof, can correlate with the metabolism at or near the target site, and therefore indicate a status (e.g., cell/tissue damage caused by the cryotherapy) at or near the target site. Therefore, on the basis of the intraprocedural signal including the temperature, the oxygen level, and/or the CO2 level, at or near the target site over time, the control component 110 may control the refrigerant delivery by the cooling assembly 140.
When the monitoring system includes a pressure sensor, the pressure sensor may measure the pressure at one or more points at or near the target site. For instance, the pressure at each of two different points at or near the target site can be monitored over time during cryotherapy, and a pressure difference over time may be determined based on the pressure at each of the two different points over time; a change in the pressure difference over time can indicate the status of the target site, or a vicinity thereof. As another example, considering that the airway is usually in proximity with the corresponding arterials, arterial pressure can be monitoring as an approximate of the pressure at or near the target site in the airway. On the basis of the intraprocedural signal including the pressure at each of the two different points and/or the pressure difference between the two different points over time, a control component (e.g., the control component 110 of
In some embodiments, the monitoring component includes one or more electrodes (e.g., an electrode pair) for measuring electrical at or near the target site. The electrical signal can include, e.g., resistance or impedance of a portion of the object at or near the target site, indicating or relating to the electrical conductivity, or a change thereof, of the portion of the object. The change in electrical conductivity can be due to a change in cell/tissue composition and/or a change in metabolism caused by, e.g., cell/tissue damage, indicating a status (including a status change) at or near the target site. On the basis of the intraprocedural signal including the electrical signal over time, the control component may control the delivery of refrigerant to the cryotherapeutic device.
In some embodiments, the intraprocedural signals may be used to provide image data providing a representation of a cold/freeze line and/or a representation of the frozen cells/tissue (e.g., appearing as an ice ball in an image). The cold/freeze line can be the interface between the frozen cells/tissue and 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 operation room to perform intraprocedural monitoring.
In various embodiments, monitoring assemblies as disclosed herein can be used to detect physiological parameters to select target sites, determine conditions during cryotherapy, and/or determine the effects of the cryotherapy. An anesthesia plan can be set to allow for spontaneous respiration before, during, and/or after an ablation procedure to intraoperatively monitor a physiological parameter, or a change thereof, before and after an ablation procedure. Such a physiological parameter, or a change thereof, may be used as an intraprocedural signal used to guide the proceeding of the ablation procedure. Examples of the physiological parameter, or a change thereof, to be monitored can include a change in the CO2 level within the airway near the target site (e.g., CO2 build up values), a change to the rate of respiration, a change in the respiratory sinus arrhythmia, a change in the metabolic activity (metabolic tracking/monitoring in which one or more metabolic parameters are tracked or monitored), the arterial pressure in the artery located in a close proximity to the target site in the airway, a cardiac plexus activity, a change in oxygenation needs from anesthesia before, after, and/or during the ablation procedure.
In various embodiments, monitoring assemblies as disclosed herein can employ an electromyography (EMG) catheter or another metallic frame with one or more sensors.
In various embodiments, the monitoring system can include an ECG catheter in the stomach or esophagus can be used to intraoperatively monitor an esophageal plexus or main vagus nerve activity. An electrical signal acquired using the ECG catheter may be used as an intraprocedural signal to guide the proceeding of an ablation procedure. For example, the ablation procedure can be stopped immediately if a modification to the esophageal ECG signal is identified.
In various embodiments, the monitoring system can include detection components used for phrenic nerve monitoring, and intraoperative monitoring can be performed by pacing main vagus nerve activity to highlight a pulmonary nerve activity, thereby better amplifying differences in the pulmonary nerve activity during and after an ablation procedure. An electrical signal corresponding to the pulmonary nerve activity may be used as an intraprocedural signal to guide the proceeding of the ablation procedure.
In various embodiments, the monitoring system can include components that provide for live imaging, e.g., a CT scanner, to monitor the freezing of cells and/or tissue at or near a target site of an object. Imaging data so acquired using an imaging device may be used as an intraprocedural signal to guide the proceeding of the ablation procedure. For instance, using live CT imaging, frozen cells and/or tissue can appear as an ice block (e.g., an ice ball) gradually change (e.g., growing) in the CT images so acquired.
In various embodiments, the monitoring system can include components that detect and/or receive information related to mechanical ventilation parameters. A change in mechanical ventilation needs during an ablation procedure, a change in respiration rate of an object being treated in the ablation procedure can be intraoperatively monitored in order to guide the proceeding of the ablation procedure. An operation parameter of a support device (e.g., a ventilation device), the respiration rate of the object, or the like, or a combination thereof, may be used as an intraprocedural signal to guide the proceeding of the ablation procedure.
The following examples are illustrative of several embodiments of the present technology.
The foregoing described embodiments depict different components contained within, or connected with, different other components. It is to be understood that such depicted architectures are merely exemplary, and that in fact many other architectures can be implemented which achieve the same functionality. In a conceptual sense, any arrangement of components to achieve the same functionality is effectively “associated” such that the desired functionality is achieved. Hence, any two components herein combined to achieve a particular functionality can be seen as “associated with” each other such that the desired functionality is achieved, irrespective of architectures or intermedial components. Likewise, any two components so associated can also be viewed as being “operably connected,” or “operably coupled,” to each other to achieve the desired functionality.
While particular embodiments of the present technology have been shown and described, it will be obvious to those skilled in the art that, based upon the teachings herein, changes and modifications may be made without departing from this technology and its broader aspects and, therefore, the appended claims are to encompass within their scope all such changes and modifications as are within the true spirit and scope of this technology. Furthermore, it is to be understood that the technology is solely defined by the appended claims. It will be understood by those within the art that, in general, terms used herein, and especially in the appended claims (e.g., bodies of the appended claims) are generally intended as “open” terms (e.g., the term “including” should be interpreted as “including but not limited to,” the term “having” should be interpreted as “having at least,” the term “includes” should be interpreted as “includes but is not limited to,” etc.). It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases “at least one” and “one or more” to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles “a” or “an” limits any particular claim containing such introduced claim recitation to technologies containing only one such recitation, even when the same claim includes the introductory phrases “one or more” or “at least one” and indefinite articles such as “a” or “an” (e.g., “a” and/or “an” should typically be interpreted to mean “at least one” or “one or more”); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should typically be interpreted to mean at least the recited number (e.g., the bare recitation of “two recitations,” without other modifiers, typically means at least two recitations, or two or more recitations).
Conjunctive language, such as phrases of the form “at least one of A, B, and C,” or “at least one of A, B and C,” (i.e., the same phrase with or without the Oxford comma) unless specifically stated otherwise or otherwise clearly contradicted by context, is otherwise understood with the context as used in general to present that an item, term, etc., may be either A or B or C, any nonempty subset of the set of A and B and C, or any set not contradicted by context or otherwise excluded that contains at least one A, at least one B, or at least one C. For example, in the illustrative example of a set having 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 of the following sets: {A}, {B}, {C}, {A, B}, {A, C}, {B, C}, {A, B, C}, and, if not contradicted explicitly or by context, any set having {A}, {B}, and/or {C} as a subset (e.g., sets with multiple “A”). Thus, such conjunctive language is not generally intended to imply that certain embodiments require at least one of A, at least one of B, and at least one of C each to be present. 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 as “at least one of A, B, and C” and “at least one of A, B and C” refer to any of the following sets: {A}, {B}, {C}, {A, B}, {A, C}, {B, C}, {A, B, C}, unless differing meaning is explicitly stated or clear from context.
This application claims the benefit of U.S. Provisional Patent Application No. 63/417,964, titled “MONITORING SYSTEMS AND METHODS FOR TARGETED LUNCH DENERVATION THERAPIES,” and filed Oct. 20, 2022, which is incorporated herein by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| 63417964 | Oct 2022 | US |
