Systems and methods for therapeutic nasal nerve modulation

Abstract

The present invention generally relates to systems and methods for therapeutically modulating nerves in or associated with the nasal region of a patient to treat rhinosinusitis.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Application No. 62 / 778,233 filed on December 11, 2018, U.S. Provisional Application No. 62 / 832,914 filed on April 12, 2019, U.S. Provisional Application No. 62 / 832,917 filed on April 12, 2019, U.S. Provisional Application No. 62 / 832,918 filed on April 12, 2019, U.S. Provisional Application No. 62 / 832,920 filed on April 12, 2019, The present invention claims priority to and the benefit of U.S. Provisional Application No. 62 / 832,923 filed on April 12, 2019, U.S. Provisional Application No. 62 / 832,925 filed on April 12, 2019, U.S. Provisional Application No. 62 / 832,927 filed on April 12, 2019, U.S. Provisional Application No. 62 / 832,928 filed on April 12, 2019, and U.S. Provisional Application No. 62 / 896,845 filed on September 6, 2019, the contents of each of which are incorporated herein by reference in their entirety. Field of the Invention

[0003] The present invention relates generally to systems and methods for treating medical conditions and, more particularly, to therapeutically modulating nerves in the nasal region of a patient to treat rhinosinusitis conditions. Background Art

[0004] Rhinitis is an inflammatory disease of the nose that is reported to affect up to 40% of the population. Rhinitis is the fifth most common chronic disease in the United States. The most common and impactful symptoms of rhinitis are nasal congestion and runny nose. Allergic rhinitis accounts for up to 65% of all rhinitis patients. Allergic rhinitis is an immune response to exposure to allergens such as airborne plant pollens, pet dander, or dust. Nonallergic rhinitis is the common occurrence of nasal congestion and runny nose. Because nonallergic rhinitis is not an immune response, its symptoms are not normally seasonal and tend to be more persistent. Symptoms of rhinitis include runny nose, sneezing, itchy nose, and nasal congestion.

[0005] In most mild cases, allergen avoidance and medication are relatively effective, but these medications require long-term use, incur costs and side effects, and are often ineffective. For example, prescription medications for rhinosinusitis have limited efficacy and undesirable side effects such as sedation, irritation, impaired taste, sore throat, dry nose, and other side effects.

[0006] There are two modern surgical options: delivering thermal energy to the inflamed soft tissue, causing tissue scarring and temporary volume loss to improve nasal airflow, and microsurgery to remove the inflamed soft tissue, thereby removing tissue to improve nasal airflow. Both options address nasal obstruction rather than runny nose and carry risks ranging from bleeding and scarring to the use of general anesthetics. Summary of the invention

[0007] The present invention recognizes that the problem with current surgical procedures is that, in order to treat rhinitis, such procedures are inaccurate and can cause significant collateral damage. The present invention solves this problem by providing a device with a unique multi-stage end effector and handle architecture that provides a high level of precise control and feedback to the operator during use of the device of the present invention. The multi-stage end effector is configured to complement the anatomical structures at multiple different locations within the nasal cavity. The handle is configured to have multiple ergonomic features and functional features that improve the use and feedback of the device, such as independent control of the deployment and energy delivery of the end effector and the shape associated with the architecture of the end effector in the deployed configuration. The handle may also include one or more markers that provide the user with a spatial orientation of the end effector when the end effector is in the nasal cavity. In that way, the present invention provides the following devices that can highly conform to anatomical changes in the nasal cavity while providing unprecedented control and guidance to the operator, so that the operator can accurately, minimally invasively and locally apply energy to one or more target sites in the nasal cavity to cause multi-point interruption of neural signals without causing collateral damage or destruction to other neural structures.

[0008] Unlike other surgical treatments for rhinitis, the device of the present invention is minimally invasive. Accordingly, the surgery can be performed in an office setting under local anesthesia. The multi-stage end effector allows for autonomic nerve supply to the nasal concha and will have a positive impact on both allergic and non-allergic rhinitis. Using this approach, it is expected that the device of the present invention will be able to provide long-term symptom relief (e.g., years rather than months). Because the treatment is accurate and the collateral damage to surrounding tissues is minimal, the patient will begin to feel symptom relief immediately after treatment. It is fully expected that after this treatment, the patient will no longer require medication.

[0009] The system and method of the present invention include a handheld device including a retractable and expandable multi-segment end effector that, once delivered to one or more target sites in the nasal cavity, can be expanded into a specific shape and / or size corresponding to the anatomical structures associated with the target sites in the nasal cavity. In particular, the end effector includes at least a first flexible segment and a second flexible segment, each of which includes a specific geometric shape when in an expanded configuration to complement the anatomical structures of the corresponding locations in the nasal cavity. Once deployed, the first segment and the second segment contact and conform to the shape of the corresponding location, including the shape that conforms to and complements one or more anatomical structures at the corresponding location. In turn, the first and second segments are accurately positioned in the nasal cavity to subsequently apply RF thermal energy to one or more target sites accurately and focusedly through one or more electrodes, thereby therapeutically regulating the associated neural structures. More specifically, the shape and size of the first and second segments when in the expanded configuration are specifically designed to contact portions of the first and second segments and therefore one or more electrodes associated therewith with target sites in the nasal cavity associated with postganglionic parasympathetic nerve fibers that innervate the nasal mucosa.

[0010] The handheld device further includes an axis operably associated with the end effector and a handle operably associated with the axis. The axis may include a predefined shape (i.e., bent or angled toward a specific orientation) to help the surgeon (or other medical professional) place the end effector at the target site. The handle includes an ergonomically designed grip portion that provides ambidextrous use for left-handed and right-handed use and conforms to the anthropometrics of the hand to allow at least one of a forehand grip and a backhand grip during use in surgery. The handle further includes a plurality of user-operated mechanisms, including at least a first mechanism for deploying the end effector from a retracted configuration to an extended deployed configuration and a second mechanism for controlling the energy output of the end effector. The user inputs of the first and second mechanisms are positioned sufficiently far from each other to allow simultaneous single-handed operation of two user inputs during surgery. Accordingly, the handle accommodates a variety of grips and provides a degree of comfort to the surgeon, thereby further improving the execution and overall outcome of the surgery. In addition, the handle and / or shaft may include markings (e.g., text, symbols, color-coded indicia, etc.) that provide the surgeon with the spatial orientation of the end effector while the end effector is in the nasal cavity. In particular, a plurality of markings may be disposed on the handle and / or shaft and provide a visual indication of the spatial orientation of one or more portions of the first and second segments of the end effector when in the deployed configuration. Thus, during initial placement of the end effector, when in the retracted configuration and enclosed within the shaft, the surgeon may rely on the markings on the handle and / or shaft as a visual indication of the spatial orientation of the end effector (e.g., linear, axial, and / or depth position), thereby ensuring that once deployed, the end effector, including both the first and second segments, is positioned at the intended location within the nasal cavity.

[0011] Thus, the handheld device of the present invention provides a user-friendly, non-invasive treatment modality for rhinosinusitis conditions, including the precise and focused application of RF thermal energy to a desired target site to therapeutically modulate the desired neural structure without causing collateral accidental damage or destruction to other neural structures. Thus, the efficacy of a vidian neurectomy procedure can be achieved using the system and method of the present invention without the above-mentioned disadvantages. Most notably, the handheld device provides surgeons with a user-friendly, non-invasive and precise method for treating runny nose and other symptoms of rhinosinusitis by targeting only those specific neural structures associated with such conditions, particularly the postganglionic parasympathetic nerves innervating the nasal mucosa, thereby disrupting the parasympathetic innervation and interrupting the parasympathetic tone. Accordingly, such treatment effectively treats rhinosinusitis conditions while greatly reducing the risk of lateral damage or destruction to other nerve fibers, thereby reducing the likelihood of unexpected complications and side effects.

[0012] One aspect of the present invention provides a device for treating a condition in a patient's nasal cavity. The device includes a multi-segment end effector for delivering energy to one or more target sites in the patient's nasal cavity. The multi-segment end effector includes a proximal segment spaced apart from a distal segment.

[0013] In some embodiments, the proximal segment includes a first set of flexible support elements arranged in a first configuration and a first set of electrodes provided by the first set of support elements and configured to deliver energy to tissue at a first target site. The distal segment includes a second set of flexible support elements arranged in a second configuration and a second set of electrodes provided by the second set of support elements and configured to deliver energy to tissue at a second target site. Each of the proximal segment and the distal segment can be transformed between a retracted configuration and an expanded deployed configuration, so that when in the expanded configuration, the first and second sets of flexible support elements are configured to position one or more of the corresponding first and second sets of electrodes at the first and second target sites. When in the expanded deployed configuration, the first set of support elements includes: a first pair of struts, each strut including an annular shape and extending upward; and a second pair of struts, each strut including an annular shape and extending downward. The second set of support elements includes a second set of struts when in the expanded deployed configuration, each strut including an annular shape extending outward to form an open-ended circumferential shape. The first and second sets of support elements include a deformable composite wire. The composite wire may include a shape memory material, such as nitinol.

[0014] In some embodiments, the first and second groups of electrodes are configured to deliver radio frequency (RF) energy to tissue at corresponding target sites within the nasal cavity, wherein the corresponding target sites are associated with parasympathetic nerve distribution. For example, the first and second groups of electrodes can be configured to deliver RF energy sufficient to therapeutically regulate the level of postganglionic parasympathetic nerves that innervate the nasal mucosa at the innervation pathways within the patient's nasal cavity. The innervation pathways can include a small hole in the patient's palatine bone. The conditions treated by the device can include, but are not limited to, allergic rhinitis, non-allergic rhinitis, chronic rhinitis, acute rhinitis, chronic sinusitis, acute sinusitis, chronic rhinosinusitis, acute rhinosinusitis, and drug-resistant rhinitis.

[0015] In some embodiments, a first segment of the multi-segment end effector has a first geometry for complementing an anatomical structure at a first location within the nasal cavity, and a second segment of the multi-segment end effector has a second geometry for complementing an anatomical structure at a second location within the nasal cavity. Each of the first segment and the second segment can be transformed between a retracted configuration and an expanded, deployed configuration, such that when the first segment is in the deployed configuration, a first set of flexible support elements of the first segment conforms to and complements the shape of the first anatomical structure at the first location, and when the second segment is in the deployed configuration, a second set of flexible support elements of the second segment conforms to and complements the shape of the second anatomical structure at the second location. The first and second anatomical structures can include, but are not limited to, the inferior turbinate, the middle turbinate, the superior turbinate, the inferior meatus, the middle meatus, the superior meatus, the pterygopalatine region, the pterygopalatine fossa, the sphenopalatine foramen, the parasphenopalatine foramen, and the sphenopalatine microforamen.

[0016] In some embodiments, the first segment of the multi-segment end effector is configured to be in an expanded configuration to fit around at least a portion of the middle turbinate in an anterior position relative to the middle turbinate, and the second segment of the multi-segment end effector is configured to be in an expanded configuration to contact multiple tissue locations in the cavity in a posterior position relative to the middle turbinate. For example, when the first segment is in an expanded configuration, the first set of flexible support elements of the first segment conforms to and complements the shape of the lateral attachment and the posterior lower edge of the middle turbinate, and when the second segment is in an expanded configuration, the second set of flexible support elements of the second segment contacts multiple tissue locations in the cavity at a posterior position relative to the lateral attachment and the posterior lower edge of the middle turbinate. Accordingly, when in an expanded configuration, the first and second segments are configured to position one or more electrodes of the corresponding first and second groups of electrodes at one or more target sites in multiple tissue locations in the cavity relative to the middle turbinate and located behind the middle turbinate. Furthermore, the first and second groups of electrodes are configured to deliver RF energy at a level sufficient to therapeutically modulate the postganglionic parasympathetic nerves that innervate the nasal mucosa at the innervation pathways within the nasal cavity of the patient.

[0017] Another aspect of the present invention provides a device for treating a condition in a patient's nasal cavity. The device includes an end effector that can be transformed between a retracted configuration and an extended deployed configuration, a shaft operably associated with the end effector, and a handle operably associated with the shaft. The handle includes a first mechanism for deploying the end effector from the retracted configuration to the extended deployed configuration and a second mechanism separate from the first mechanism for controlling the energy output of the end effector.

[0018] In some embodiments, the handle includes an ergonomically designed grip portion including a shape, size, and profile that provides ambidextrous use for both left-handed and right-handed use and conforms to hand anthropometrics to allow at least one of an overhand grip and a reverse hand grip during use in surgery. The user input for the first mechanism may be positioned at a top portion of the handle adjacent to the grip portion, while the user input for the second mechanism is positioned at a side portion of the handle adjacent to the grip portion. The user inputs for the first and second mechanisms may be positioned sufficiently far from each other to allow simultaneous single-handed operation of both user inputs during surgery.

[0019] In some embodiments, the first mechanism includes a rack and pinion assembly that provides movement of the end effector between a retracted configuration and a deployed configuration in response to input from a user-operated controller. The rack and pinion assembly may include a set of gears for receiving input from the user-operated controller and converting the input into linear motion of a rack member operably associated with at least one of the shaft and the end effector. The rack and pinion assembly may include a gear ratio sufficient to balance the stroke length and the retraction and deployment forces, thereby improving control of deployment of the end effector.

[0020] In some embodiments, the user-operated controller includes a slider mechanism operably associated with the rack and pinion track assembly, wherein movement of the slider mechanism in a rearward direction toward the proximal end of the handle causes the end effector to transition to an deployed configuration, and movement of the slider mechanism in a forward direction toward the distal end of the handle causes the end effector to transition to a retracted configuration.

[0021] In some embodiments, the user-operated controller includes a roller mechanism operably associated with the rack and pinion track assembly, wherein rotation of the wheel in a rearward direction toward the proximal end of the handle causes the end effector to transition to a deployed configuration, and rotation of the wheel in a forward direction toward the distal end of the handle causes the end effector to transition to a retracted configuration.

[0022] In some embodiments, the second mechanism includes a user-operated controller that is configured to be actuated between an effective position and an ineffective position to control the delivery of energy from the end effector. The user-operated controller can be multi-mode in that the user-operated controller can be actuated between multiple positions that provide different functions / modes. For example, based on a single user input (i.e., a single press of an associated button within the controller), the second mechanism can provide a baseline juxtaposition / sensing check function before adjustment. After pressing and holding the controller button for a predefined period of time, the energy output of the end effector can be activated. Further, after double-clicking the controller button, the energy output is stopped.

[0023] In some embodiments, the handle may include a shape associated with the architecture of the end effector in the deployed configuration. For example, the handle may generally include a grip portion whose shape provides a user with physical confirmation of the orientation of the portion of the end effector when in the deployed configuration. For example, the end effector may include a first segment spaced apart from a second segment, wherein each of the first segment and the second segment is transformable between a retracted configuration and an extended deployed configuration. The handle includes a grip portion, the grip portion including a top, a bottom, a side, a proximal end, and a distal end, wherein, when in the deployed configuration, at least one of the top, the bottom, and the side of the grip portion of the handle is associated with the architecture of at least one of the first segment and the second segment of the end effector. For example, the first segment may include a first set of flexible support elements and the second segment may include a second set of flexible support elements. When in the extended deployed configuration, the first set of support elements may include: a first pair of struts, each strut including an annular shape and extending upward; and a second pair of struts, each strut including an annular shape and extending downward. For example, the top of the grip portion may be associated with the first pair of struts extending upward, and the bottom of the grip portion may be associated with the second pair of struts extending downward. When in the expanded configuration, the second set of support elements may include a second set of struts, each strut including an annular shape extending outwardly to form an open-ended circumferential shape. The distal end of the grip portion may be associated with the second set of outwardly extending struts.

[0024] In some embodiments, the handle and / or shaft may include one or more markings that provide the user with a spatial orientation of the end effector when the end effector is in the nasal cavity. For example, one or more markings on the handle or shaft may provide a visual indication of the orientation of one or more parts of the end effector, specifically an indication of the spatial orientation of one or both of the first segment and the second segment when in the expanded configuration. The marking may include any visual marking, such as text, symbols, and color-coded markings. In some embodiments, multiple markings may be set to provide a visual indication of one or more parts of the first segment and the second segment when in the expanded configuration. For example, a first marking on one or both of the handle and the shaft may be associated with a first pair of struts extending upwardly of the first segment of the end effector, and a second marking may be associated with a second pair of struts extending downwardly of the first segment of the end effector. In this way, when the first segment is in the expanded configuration in the nasal cavity, the first marking provides the user with a visual indication of the spatial orientation of the first pair of struts extending upwardly, and the second marking provides the user with a visual indication of the spatial orientation of the second pair of struts extending downwardly.

[0025] Another aspect of the present invention provides a method for treating a condition in a nasal cavity of a patient. The method includes a propulsion device including a multi-segment end effector for delivering energy to one or more target sites in the nasal cavity of the patient. The multi-segment end effector includes a proximal segment spaced apart from a distal segment. The method further includes delivering energy to tissue at the one or more target sites through the proximal segment and the distal segment.

[0026] In some embodiments, the proximal segment includes a first set of flexible support elements arranged in a first configuration and a first set of electrodes provided by the first set of support elements and configured to deliver energy to tissue at a first target site. The distal segment includes a second set of flexible support elements arranged in a second configuration and a second set of electrodes provided by the second set of support elements and configured to deliver energy to tissue at a second target site. Each of the proximal segment and the distal segment can be transformed between a retracted configuration and an expanded deployed configuration, so that when in the expanded configuration, the first and second sets of flexible support elements are configured to position one or more of the corresponding first and second sets of electrodes at the first and second target sites. When in the expanded deployed configuration, the first set of support elements includes: a first pair of struts, each strut including an annular shape and extending upward; and a second pair of struts, each strut including an annular shape and extending downward. The second set of support elements includes a second set of struts when in the expanded deployed configuration, each strut including an annular shape extending outward to form an open-ended circumferential shape. The first and second sets of support elements include a deformable composite wire and may include a shape memory material, such as nitinol.

[0027] In some embodiments, the method further comprises deploying the proximal and distal segments of the multi-segment end effector at respective first and second target sites, thereby positioning one or more electrodes of respective first and second sets of electrodes at the first and second target sites. Delivering energy through the proximal and distal segments comprises delivering (RF) energy through the respective first and second sets of electrodes at a level sufficient to therapeutically modulate postganglionic parasympathetic nerves innervating the nasal mucosa at innervated pathways within the nasal cavity of the patient.

[0028] In some embodiments, a first segment of the end effector has a first geometry for complementing an anatomical structure at a first location within the nasal cavity, and a second segment of the end effector has a second geometry for complementing an anatomical structure at a second location within the nasal cavity. Accordingly, the method may include deploying the first segment and the second segment at respective first and second locations within the nasal cavity, and delivering energy to tissue at one or more target sites relative to the first and second locations through the first and second segments.

[0029] In some embodiments, when the first segment is in the expanded configuration, the first set of flexible support elements of the first segment conforms to and complements the shape of a first anatomical structure at a first location, and when the second segment is in the expanded configuration, the second set of flexible support elements of the second segment conforms to and complements the shape of a second anatomical structure at a second location. The first and second anatomical structures may include, but are not limited to, the inferior turbinate, the middle turbinate, the superior turbinate, the inferior meatus, the middle meatus, the superior meatus, and the sphenopalatine foramen.

[0030] In some embodiments, the first segment of the end effector is configured to be in an expanded configuration to fit around at least a portion of the middle turbinate in an anterior position relative to the middle turbinate, and the second segment of the end effector is configured to be in an expanded configuration to contact multiple tissue locations in the cavity in a posterior position relative to the middle turbinate. For example, when the first segment is in an expanded configuration, the first set of flexible support elements of the first segment conforms to and complements the shape of the lateral attachment portion of the middle turbinate in the anterior position, and when the second segment is in an expanded configuration, the second set of flexible support elements of the second segment conforms to and complements the shape of at least a second anatomical structure in the cavity behind the lateral attachment portion of the middle turbinate. Accordingly, when in an expanded configuration, the first and second segments are configured to position one or more electrodes of the corresponding first and second sets of electrodes at one or more target sites in multiple tissue locations in the cavity behind the middle turbinate and located. In turn, the first and second sets of electrodes deliver RF energy at a level sufficient to therapeutically modulate the postganglionic parasympathetic nerves that innervate the nasal mucosa at the innervation pathways within the patient's nasal cavity.

[0031] Another aspect of the present invention provides a method for treating a condition in a patient's nasal cavity. The method includes providing a treatment device, the treatment device including an end effector that can be transformed between a retracted configuration and an extended deployed configuration, an axis operably associated with the end effector, and a handle operably associated with the axis. The handle includes a first mechanism for deploying the end effector from the retracted configuration to the extended deployed configuration and a second mechanism separate from the first mechanism for controlling the energy output of the end effector. The method includes advancing the end effector to one or more target sites in the patient's nasal cavity, the end effector being configured to deliver energy to the one or more target sites in the nasal cavity. The method further includes deploying the end effector at the one or more target sites through user input of the first mechanism on the handle, and delivering energy from the end effector to tissue at the one or more target sites through user input of the second mechanism.

[0032] In some embodiments, the handle includes a shape associated with the architecture of the end effector in the deployed configuration. For example, the handle may generally include a grip portion whose shape provides a user with physical confirmation of the orientation of a portion of the end effector when in the deployed configuration. Thus, during advancement of the end effector to one or more target sites within the nasal cavity, the method further includes positioning the end effector at the one or more target sites based at least in part on the orientation of the handle.

[0033] In some embodiments, the handle and / or shaft may include one or more markings that provide the user with a spatial orientation of the end effector when the end effector is in the nasal cavity. For example, one or more markings on the handle or shaft may provide a visual indication of the orientation of one or more parts of the end effector, specifically an indication of the spatial orientation of one or both of the first segment and the second segment of the end effector in the deployed configuration. The markings may include any visual markings, such as text, symbols, and color-coded markings. In some embodiments, multiple markings may be set to provide a visual indication of one or more portions of the first segment and the second segment when in the deployed configuration. Therefore, during the advancement of the end effector to one or more target locations within the nasal cavity, the method further includes positioning the end effector at the one or more target locations based at least in part on the orientation of the handle or shaft and one or more markings surrounding the handle or shaft.

[0034] Another aspect of the present invention provides a device for treating a condition within a patient's nasal cavity. The device includes a multi-segment end effector, the multi-segment end effector including at least a first retractable and expandable segment, the first retractable and expandable segment including a microelectrode array arranged around a plurality of struts. When the first segment is in an expanded state, the plurality of struts have a bilateral geometry that conforms to and accommodates the anatomical structure within the nasal cavity. In particular, when in the expanded state, the plurality of struts contact a plurality of locations along a plurality of portions of the anatomical structure, and the electrodes of the microelectrode array are configured to emit energy at a level sufficient to form a plurality of microlesions in the tissue to mucus production and / or mucosal congestion elements.

[0035] In some embodiments, the bilateral geometry includes at least a first strut that conforms to and accommodates a first side of the anatomical structure when the first segment is in an expanded state and at least a second strut that conforms to and accommodates a second side of the anatomical structure. When the first segment is in an expanded state, the first strut contacts a plurality of locations along the first side of the anatomical structure, and a first set of electrodes of a microelectrode array provided by the first strut is configured to emit energy at a level sufficient to produce a plurality of corresponding microlesions in tissue along the first side of the anatomical structure. Similarly, when the first segment is in an expanded state, the second strut contacts a plurality of locations along the second side of the anatomical structure, and a second set of electrodes of a microelectrode array provided by the second strut is configured to emit energy at a level sufficient to produce a plurality of corresponding microlesions in tissue along the second side of the anatomical structure. The anatomical structure may include, but is not limited to, the inferior turbinate, the middle turbinate, the superior turbinate, the inferior meatus, the middle meatus, the superior meatus, the pterygopalatine region, the pterygopalatine fossa, the sphenopalatine foramen, the parasphenopalatine foramen, and the sphenopalatine microforamen.

[0036] In some embodiments, each of the first and second pillars has an annular shape and extends in an outward direction away from each other. The first and second pillars include a deformable composite wire, and the composite wire includes a shape memory material. Each pillar can include a plurality of electrodes of an electrode array positioned at separate and discrete portions of the pillar. In this way, when in an expanded state, each pillar can position at least one associated electrode of the microelectrode array to contact tissue at a separate corresponding position on a corresponding side of the anatomical structure to deliver energy thereto. The electrodes of the microelectrode array are configured to be independently activated and controlled, thereby delivering energy independently of each other.

[0037] Another aspect of the present invention provides a system for treating a condition within a patient's nasal cavity. The system includes a device including a multi-segment end effector for delivering energy to one or more target sites within the patient's nasal cavity and further sensing one or more characteristics of the one or more target sites. The multi-segment end effector includes a proximal segment spaced apart from a distal segment, wherein each of the proximal segment and the distal segment has a specific geometry for complementing anatomical structures associated with the one or more target sites at corresponding locations within the nasal cavity. The system further includes a console unit operably associated with the device and configured to receive data from the device associated with one or more characteristics of the one or more target sites and process the data to provide information related to the one or more target sites to an operator.

[0038] The console unit is configured to provide information associated with at least one of: identification and location of target and non-target neural structures at one or more target sites prior to therapeutic modulation treatment provided by at least one of the proximal and distal segments of the end effector; identification and location of target and non-target anatomical structures at one or more target sites prior to therapeutic modulation treatment provided by at least one of the proximal and distal segments of the end effector; real-time feedback associated with the efficacy of the therapeutic modulation treatment on one or more target neural and / or anatomical structures during the therapeutic modulation treatment; and feedback associated with the efficacy of the therapeutic modulation treatment on one or more target neural and / or anatomical structures during the therapeutic modulation treatment.

[0039] In some embodiments, each of the proximal and distal segments of the end effector includes a flexible strut and a plurality of elements provided by the strut.

[0040] For example, a first subset of the plurality of elements may be configured to deliver non-therapeutic stimulation energy to tissue at one or more target sites at a frequency for locating at least one of a target neural structure, a non-target neural structure, a target anatomical structure, and a non-target anatomical structure. A second subset of the plurality of elements may be configured to sense a characteristic of at least one of the target neural structure, the non-target neural structure, the target anatomical structure, and the non-target anatomical structure in response to the stimulation energy. The characteristic may include, but is not limited to, at least one of a physiological characteristic, a bioelectric characteristic, and a thermal characteristic. The bioelectric characteristic may include, but is not limited to, at least one of a complex impedance, a resistance, a reactance, a capacitance, an inductance, a dielectric constant, a conductivity, a neural firing voltage, a neural firing current, a depolarization, a hyperpolarization, a magnetic field, and an induced electromotive force.

[0041] In some embodiments, the proximal segment of the end effector includes a first set of flexible struts arranged in a first configuration, and the distal segment of the end effector includes a second set of flexible struts arranged in a second configuration. Each of the proximal segment and the distal segment can be transformed between a retracted configuration and an expanded deployed configuration, such that when the proximal segment is in the deployed configuration, the first set of flexible struts conforms to and complements the shape of a first anatomical structure at a first position, and when the distal segment is in the deployed configuration, the second set of flexible struts conforms to and complements the shape of a second anatomical structure at a second position. The first and second anatomical structures can include, but are not limited to, the inferior turbinate, the middle turbinate, the superior turbinate, the inferior meatus, the middle meatus, the superior meatus, the pterygopalatine region, the pterygopalatine fossa, the sphenopalatine foramen, the parasphenopalatine foramen, and the sphenopalatine microforamen.

[0042] The first group of flexible struts and the second group of flexible struts can be configured to position one or more of the respective plurality of elements provided by each at the corresponding one or more target sites when in the expanded configuration. For example, when in the expanded configuration, the first group of flexible struts can include: a first pair of struts, each strut including an annular shape and extending upward; and a second pair of struts, each strut including an annular shape and extending downward. When in the expanded configuration, the second group of flexible struts can include a second group of struts, each strut including an annular shape extending outward to form a circumferential shape with open ends. As such, the first and second groups of flexible struts can generally include a deformable composite wire, wherein the composite wire includes a shape memory material.

[0043] In some embodiments, the console unit is configured to detect and / or map the location of at least one of a target neural structure, a non-target neural structure, a target anatomical structure, and a non-target anatomical structure, and to control the delivery of therapeutic energy from at least one of the proximal segment and the distal segment of the end effector in an adjustment mode based on the location of at least one of the target neural structure, the non-target neural structure, the target anatomical structure, and the non-target anatomical structure. At least some of the elements provided by at least one of the proximal segment and the distal segment are configured to deliver energy at a level sufficient to therapeutically modulate one or more nerves associated with the location of the target neural structure and / or the target anatomical structure, while avoiding the location of the non-target neural structure and / or the non-target anatomical structure. At least some of these elements are configured to deliver energy at a level insufficient to therapeutically modulate the non-target neural structure and / or the non-target anatomical structure based on the adjustment mode.

[0044] In some embodiments, the console unit includes a controller configured to selectively control energy output of elements of the proximal and / or distal segments of the end effector, wherein some of the elements are configured to be independently activated and controlled to deliver energy independently of each other. The controller can be configured to adjust the energy output of the elements of the proximal and / or distal segments of the end effector during therapeutic modulation based at least in part on real-time feedback associated with the effectiveness of therapeutic modulation treatment of one or more target anatomical and / or neural structures.

[0045] Another aspect of the present invention provides a method for treating a condition in a patient's nasal cavity. The method includes providing a treatment device including a multi-segment end effector and a visual marker, the multi-segment end effector including a proximal segment spaced apart from a distal segment. The method further includes advancing the proximal segment and the distal segment through the patient's nasal cavity and past the middle turbinate under image guidance and deploying the distal segment from a retracted configuration to an expanded configuration. The proximal segment is then aligned relative to the middle turbinate under image guidance and with reference to the visual marker. After alignment, the method includes deploying the proximal segment around the middle turbinate. The method further includes advancing the deployed proximal segment toward the middle turbinate to establish contact and securing the proximal segment to the middle turbinate.

[0046] The deployed proximal segment has a shape that complements the shape of the middle turbinate and / or the geometry of the lateral attachment portion of the middle turbinate, thereby ensuring that the deployed proximal segment is fixed to the middle turbinate and / or the lateral attachment portion of the middle turbinate. For example, in some embodiments, the proximal segment includes a set of flexible support elements that conform to and complement the shape of the middle turbinate and / or the lateral attachment portion of the middle turbinate when the proximal segment is in the expanded deployed configuration.

[0047] The method may further include delivering energy to the middle turbinate and / or the lateral attachment of the middle turbinate and / or the lateral wall of the nasal cavity through the proximal segment to treat the condition. The condition may include, but is not limited to, allergic rhinitis, non-allergic rhinitis, chronic rhinitis, acute rhinitis, chronic sinusitis, acute sinusitis, chronic rhinosinusitis, acute rhinosinusitis and drug-resistant rhinitis, and combinations thereof. In some embodiments, delivering energy from the proximal segment includes delivering radio frequency (RF) energy to the tissue of the lateral wall around the middle turbinate at one or more target sites through one or more electrodes provided by the proximal segment, wherein the one or more target sites are associated with one or more neurogenic pathways. In some embodiments, the RF energy of the level sufficient to destroy one or more neurogenic pathways associated with the condition, such as the neurogenic pathways causing runny nose and / or nasal congestion, is delivered through one or more electrodes provided by the proximal segment. In other embodiments, the RF energy of the level sufficient to therapeutically regulate the postganglionic parasympathetic nerves of the nerve innervating the nasal mucosa at the neurogenic pathway is delivered through one or more electrodes provided by the proximal segment.

[0048] In some embodiments, the visual marker is provided by a shaft operably associated with the multi-segment end effector. The visual marker provides a visual indication of the spatial orientation of one or more portions of the proximal segment. The visual marker may include, for example, text, symbols, color-coded indicia, etc. In some embodiments, the step of aligning the proximal segment relative to the middle turbinate includes positioning the shaft and associated visual marker relative to the middle turbinate and / or the posterior lateral attachment of the middle turbinate and / or the lateral nasal wall under image guidance.

[0049] Another aspect of the present invention provides a system for treating a condition in a patient's nasal cavity. The system includes a treatment device and an image guidance component for providing a visual depiction of one or more portions of the treatment device to assist a user (i.e., a surgeon or other medical professional) in performing a procedure for treating the patient's nasal condition.

[0050] The treatment device includes a multi-segment end effector including a proximal segment spaced apart from a distal segment, a shaft operably associated with the multi-segment end effector, and a handle operably associated with the multi-segment end effector and the shaft. The shaft includes one or more visual markers for providing a user with a visual indication of the spatial orientation of at least the proximal segment under image guidance when the multi-segment end effector is within a nasal cavity of a patient. The handle includes a controller mechanism for providing independent, controlled deployment of each of the proximal segment and the distal segment from a retracted configuration to an expanded configuration within the nasal cavity. The image guidance assembly provides a visual depiction of at least the shaft and the visual markers relative to the surrounding anatomical structures of the nasal cavity, thereby assisting the user in deploying and positioning at least the proximal segment within the nasal cavity.

[0051] In some embodiments, at least one visual marker is associated with the spatial orientation of a portion of the proximal segment when the proximal segment is in the expanded configuration. The visual marker may include, for example, text, symbols, color-coded indicia, and the like.

[0052] When in the expanded configuration, the proximal segment may include a geometry that complements the shape of the middle turbinate and / or the lateral attachment portion of the middle turbinate, thereby ensuring that the deployed proximal segment can establish sufficient contact with and securely engage the lateral attachment portion of the middle turbinate and / or the middle turbinate. For example, the proximal segment may include a set of flexible support elements that conform to and complement the shape of the lateral attachment portion of the middle turbinate and / or the middle turbinate when the proximal segment is in the expanded, deployed configuration. The distal segment may include a geometry that complements the shape of another anatomical structure within the nasal cavity when in the expanded configuration.

[0053] In some embodiments, the controller mechanism includes a rack and pinion assembly that provides movement of at least one of the proximal segment and the distal segment between the retracted configuration and the extended configuration in response to user input from an associated user-operated controller. The rack and pinion assembly may include, for example, a set of gears for receiving user input from the user-operated controller and converting the user input into linear motion of a rack member operably associated with the multi-segment end effector.

[0054] In some embodiments, the controller mechanism may further include a detent feature positioned relative to the proximal segment and the distal segment and configured to provide a user with effective feedback indicating the deployment of at least one of the proximal segment and the distal segment. The effective feedback may be in the form of tactile feedback provided by the controller mechanism. For example, the tactile feedback may include an increase or decrease in resistance associated with the user input of the controller mechanism for corresponding movement of at least one of the proximal segment and the distal segment between the retracted configuration and the extended configuration and / or configurations therebetween (i.e., multiple configurations between the fully retracted configuration and the fully extended configuration).

[0055] In some embodiments, the controller mechanism may further include a friction-based feature configured to provide stable movement of at least one of the proximal segment and the distal segment between the retracted configuration and the extended configuration, and further provide effective feedback to the user indicating the deployment of at least one of the proximal segment and the distal segment. The friction-based feature may include a lock mechanism that provides constant friction between one or more parts of the rack and pinion assembly, which is sufficient to maintain the position of at least one of the proximal segment and the distal segment during its deployment. For example, regardless of whether the user maintains contact with the user-operated controller, the constant friction can be sufficient to maintain the segment in a certain position when either the proximal segment or the distal segment is transformed between the retracted configuration and the extended configuration. In other words, the user does not need to maintain contact with the user-operated controller to ensure that the proximal segment or the distal segment maintains a certain position during its deployment. Instead, the user can interact with the user-operated controller to transform one of the proximal segment and the distal segment into a desired configuration, and the constant friction provided by the locking mechanism is sufficient to maintain the configuration of the proximal segment or the distal segment when the user's hand is released (i.e., any contact with the user-operated controller is removed). The level of constant friction is sufficient to prevent undesired movement of the proximal or distal segments (i.e., unintentional collapse or expansion) while still allowing the user to overcome such friction to move the proximal or distal segments to a desired configuration based on user input of a user-operated controller.

[0056] In some embodiments, the user-operated controller includes a slider mechanism operably associated with the rack and pinion track assembly, wherein movement of the slider mechanism in a first direction causes at least one of the proximal segment and the distal segment to transition to an extended configuration, and movement of the slider mechanism in a second, opposite direction causes at least one of the proximal segment and the distal segment to transition to a retracted configuration.

[0057] In other embodiments, the user-operated controller includes a roller mechanism operably associated with the rack and pinion track assembly, wherein rotation of the wheel in a first direction causes at least one of the proximal segment and the distal segment to transition to an extended configuration, and rotation of the wheel in a second, opposite direction causes at least one of the proximal segment and the distal segment to transition to a retracted configuration. BRIEF DESCRIPTION OF THE DRAWINGS

[0058] Figure 1A and Figure 1B is a diagrammatic illustration of a therapeutic neuromodulation system for treating a condition within the nasal cavity using a handheld device, according to some embodiments of the present disclosure.

[0059] Figure 2 is a diagrammatic illustration of a console coupled to a handheld neuromodulation device consistent with the present disclosure, further illustrating a multi-segment end effector of the handheld device for delivering energy to tissue at one or more target sites within a nasal cavity via a proximal segment and a distal segment.

[0060] Figure 3A is a cutaway side view showing the anatomy of the lateral nasal wall.

[0061] Figure 3B yes Figure 1A Magnified lateral view of the nerves of the lateral nasal wall.

[0062] Figure 3C is an anterior view of the left palatine bone, demonstrating the geometry of the foramina in the left palatine bone.

[0063] Figure 4 is a side view of one embodiment of a handheld device for providing therapeutic nasal nerve modulation consistent with the present disclosure.

[0064] Figure 5A is an enlarged perspective view of a multi-segment end effector showing a first (proximal) segment and a second (distal) segment.

[0065] Figure 5B It is an exploded perspective view of a multi-stage end effector.

[0066] Figure 5C It is an enlarged top view of the multi-segment end effector.

[0067] Figure 5D It is an enlarged side view of the multi-segment end effector.

[0068] Figure 5E is an enlarged (facing proximally) front view of a first (proximal) segment of a multi-segment end effector.

[0069] Fig. 5F is an enlarged (facing proximally) front view of the second (distal) segment of the multi-segment end effector.

[0070] Figure 6 A partial cross-sectional perspective view of a portion of a support element showing exposed conductive wires used as energy delivery elements or electrode elements.

[0071] Figure 7 is along Figure 4 A cross-sectional view of a portion of the axis of the handheld device taken along line 7-7.

[0072] Figure 8 is a side view of the handle of the handheld device.

[0073] Fig. 9 is a side view of the handle showing the internal components enclosed within.

[0074] Fig.10 is a side view of the handle illustrating a plurality of markings on a portion of the handle for providing a user with spatial orientation of the end effector when the end effector is in the nasal cavity.

[0075] Fig.11 is a perspective view of a shaft illustrating a plurality of markings on a distal portion of the shaft for providing a user with spatial orientation of the end effector when the end effector is in the nasal cavity.

[0076] Fig.12 is a partial cutaway side view illustrating a method for delivering an end effector to a target site in the nasal region according to an embodiment of the present disclosure.

[0077] Fig.13 is a flow chart illustrating one embodiment of a method for treating a condition within the nasal cavity of a patient.

[0078] Fig.14 is a flow chart illustrating another embodiment of a method for treating a condition within the nasal cavity of a patient.

[0079] Fig.15 is a flow chart illustrating another embodiment of a method for treating a condition within the nasal cavity of a patient. DETAILED DESCRIPTION

[0080] Various conditions related to the nasal cavity may affect breathing and other functions of the nose. One of the more common conditions is rhinitis, which is defined as inflammation of the nasal mucosa. Symptoms of rhinitis include nasal obstruction, blockage, nasal congestion, nasal discharge (e.g., runny nose and / or postnasal drip), facial pain, facial pressure, and / or decreased or complete loss of smell and / or taste. Sinusitis is another common condition that involves inflammation or swelling of the tissue lining the sinuses, which may lead to subsequent conditions. Rhinitis and sinusitis are often associated with each other because rhinitis usually precedes sinusitis. Therefore, the term "rhinosinusitis" is often used to describe both conditions.

[0081] Rhinosinusitis can be classified into different subtypes, depending on the duration and type of the system, including allergic rhinitis, non-allergic rhinitis, chronic rhinitis, acute rhinitis, recurrent rhinitis, chronic sinusitis, acute sinusitis, recurrent sinusitis and resistant rhinitis and / or sinusitis, in addition to a combination of one or more of the aforementioned conditions. It should be noted that acute rhinosinusitis conditions are conditions with symptoms lasting less than twelve weeks, while chronic rhinosinusitis conditions are those lasting more than twelve weeks.

[0082] A recurrent rhinosinusitis condition is defined as four or more episodes of acute rhinosinusitis within a 12-month period with resolution of symptoms between each episode. Rhinosinusitis has many environmental and biological causes. For example, non-allergic rhinosinusitis can be caused by environmental irritants, medications, foods, hormonal changes, and / or a deviated nasal septum. Causes of allergic rhinitis may include exposure to seasonal allergens, perennial allergens occurring at any time of the year, and / or occupational allergens. Accordingly, rhinosinusitis affects millions of people and is the primary reason patients seek medical care.

[0083] The present invention provides systems and methods for therapeutically modulating nerves in the nasal region of a patient to effectively treat rhinosinusitis conditions. In particular, aspects of the present invention include systems and methods for performing accurate, minimally invasive, and localized energy application to one or more target sites within the nasal cavity to disrupt parasympathetic motor sensory function associated with rhinosinusitis conditions without causing collateral damage or destruction to other neural structures.

[0084] It should be noted that although many embodiments are described in conjunction with devices, systems, and methods for therapeutically modulating nerves in the nasal region to treat rhinitis, other applications and other embodiments in addition to the applications and embodiments described herein are also within the scope of the present disclosure. For example, at least some embodiments of the present disclosure can be used to treat other indications, such as treating chronic sinusitis and epistaxis. In particular, the embodiments described herein can be configured to treat allergic rhinitis, non-allergic rhinitis, chronic rhinitis, acute rhinitis, chronic sinusitis, acute sinusitis, chronic rhinosinusitis, acute rhinosinusitis, and / or drug-resistant rhinitis.

[0085] Figure 1A and Figure 1B is a diagrammatic illustration of a therapeutic neuromodulation system 100 for treating a condition within the nasal cavity using a handheld device 102, according to some embodiments of the present disclosure. The system 100 generally includes a neuromodulation device 102 and a neuromodulation console 104 to which the device 102 is to be connected. Figure 21 is a diagrammatic illustration of a console 104 coupled to a handheld neuromodulation device 102. As shown, the neuromodulation device 102 is a handheld device that includes a retractable and extendable multi-segment end effector 114, a shaft 116 operably associated with the end effector 114, and a handle 118 operably associated with the shaft 116. The end effector 114 is configured to be advanced into the nasal cavity of the patient 12 and positioned at a location associated with one or more target sites for therapeutic neuromodulation treatment. It should be noted that the terms "end effector" and "treatment assembly" may be used interchangeably throughout this disclosure.

[0086] For example, a surgeon or other medical professional performing an operation can manipulate the shaft 116 and push the shaft into the nasal cavity using the handle 118, wherein the shaft 116 is configured to position at least its distal portion in the lumen at a treatment site or target site within the nasal region. One or more target sites can generally be associated with postganglionic parasympathetic nerve fibers that innervate the nasal mucosa. The target site can be an area, volume, or zone where the target nerve is located, and can be different in size and shape according to the patient's anatomical structure. Once positioned, the end effector 114 can be deployed and then energy can be delivered to one or more target sites, thereby therapeutically regulating the relevant nerves, particularly the nerves associated with the rhinosinusitis condition, so as to treat this condition. For example, the end effector 114 can include at least one energy delivery element configured to therapeutically regulate the postganglionic parasympathetic nerve, such as an electrode. For example, one or more electrodes can be provided by one or more parts of the end effector 114, wherein the electrode can be configured to apply electromagnetic nerve regulation energy (e.g., radio frequency (RF) energy) to the target site. In other embodiments, the end effector 114 may include other energy delivery elements configured to provide therapeutic neuromodulation using various other modalities, such as cryotherapeutic cooling, ultrasound energy (e.g., high-intensity focused ultrasound (“HIFU”) energy), microwave energy (e.g., via a microwave antenna), direct heating, high and / or low power laser energy, mechanical vibration, and / or optical power.

[0087] In some embodiments, the end effector 114 may include one or more sensors (not shown), such as one or more temperature sensors (e.g., thermocouples, thermistors, etc.), impedance sensors, and / or other sensors. The sensors and / or electrodes may be connected to one or more wires extending through the shaft 116 and configured to transmit signals to and / or from the sensors and / or transmit energy to the electrodes.

[0088] As shown, the device 102 is operably coupled to the console 104 via a wired connection, such as a cable 120. However, it should be noted that the device 102 and the console 104 may be operably coupled to each other via a wireless connection. The console 104 is configured to provide various functions for the neuromodulation device 102, which may include, but are not limited to, controlling, monitoring, supplying, and / or otherwise supporting the operation of the neuromodulation device 102. For example, when the neuromodulation device 102 is configured for electrode-based, thermal element-based, and / or transducer-based therapy, the console 104 may include an energy generator 106 configured to generate radio frequency (RF) energy (e.g., monopolar, bipolar, or multi-stage RF energy), pulsed electrical energy, microwave energy, light energy, ultrasound energy (e.g., ultrasound and / or HIFU delivered intraluminally), direct thermal energy, radiation (e.g., infrared, visible light, and / or gamma radiation), and / or another suitable type of energy.

[0089] In some embodiments, the console 104 may include a controller 107 that is communicatively coupled to the neuromodulation device 102. However, in the embodiments described herein, the controller 107 may generally be carried by and disposed within the handle 118 of the neuromodulation device 102. The controller 107 is configured to initiate, terminate, and / or adjust the operation of one or more electrodes provided by the end effector 114 directly and / or through the console 104. For example, the controller 107 may be configured to execute an automatic control algorithm and / or receive control instructions from an operator (e.g., a surgeon or other medical professional or clinician). For example, the controller 107 and / or other components of the console 104 (e.g., a processor, memory, etc.) may include a computer-readable medium that carries instructions that, when executed by the controller 107, cause the device 102 to perform certain functions (e.g., apply energy in a particular manner, detect impedance, detect temperature, detect nerve location or anatomical structure, etc.). The memory includes one or more of a variety of hardware devices for volatile and non-volatile storage, and may include read-only and writable memory. For example, memory may include random access memory (RAM), CPU registers, read-only memory (ROM), and writable non-volatile memory such as flash memory, hard drives, floppy disks, CDs, DVDs, magnetic storage devices, tape drives, device buffers, etc. Memory is not a propagating signal separate from the underlying hardware; therefore, memory is non-transitory.

[0090] The console 104 can be further configured to provide feedback to the operator before, during, and / or after the treatment procedure via the evaluation / feedback algorithm 110. For example, the evaluation / feedback algorithm 110 can be configured to provide information associated with the tissue temperature of the treatment site, the location of the nerves at the treatment site, and / or the effect of therapeutic neuromodulation on the nerves at the treatment site. In certain embodiments, the evaluation / feedback algorithm 110 can include features for confirming the efficacy of the treatment and / or enhancing the desired performance of the system 100. For example, the evaluation / feedback algorithm 110 in conjunction with the controller 107 can be configured to monitor the temperature of the treatment site during treatment and automatically shut off energy delivery when the temperature reaches a predetermined maximum value (e.g., when RF energy is applied) or reaches a predetermined minimum value (e.g., when cryotherapy is applied). In other embodiments, the evaluation / feedback algorithm 110 in conjunction with the controller 107 can be configured to automatically terminate treatment after reaching a predetermined maximum time, a predetermined maximum impedance rise of the target tissue (i.e., a predetermined maximum impedance of the target tissue compared to a baseline impedance measurement), and / or other thresholds of biomarkers associated with autonomic function. This and other information associated with the operation of the system 100 may be communicated to the operator via a graphical user interface (GUI) 112, which is provided via a display on the console 104 and / or a separate display (not shown), such as a tablet or monitor, communicatively coupled to the console 104. The GUI 112 may generally provide operating instructions for the procedure, such as directing the operator to select a nasal cavity to be treated, indicating when the device 102 is primed and ready to perform treatment, and further providing status of the treatment during the procedure, including indicating when the treatment is complete.

[0091] For example, in some embodiments, the end effector 114 and / or other portions of the system 100 may be configured to detect various parameters of the heterogeneous tissue of the target site to determine the anatomical structure (e.g., tissue type, tissue location, vasculature, bone structure, foramen, sinuses, etc.) at the target site, locate nerves and / or other structures, and allow for nerve mapping. For example, the end effector 114 may be configured to detect impedance, dielectric properties, temperature, and / or other properties indicative of the presence of nerve fibers in the target area. As shown in FIG. 1 , the console 104 may further include a monitoring system 108 configured to receive detected electrical and / or thermal measurements of the tissue of the target site taken by the end effector 114 and specifically sensed by appropriate sensors (e.g., temperature sensors and / or impedance sensors), and process this information to identify the presence of nerves at the target site, the location of the nerves, and / or the activity of the nerves. The nerve monitoring system 108 may be operably coupled to the electrodes and / or other features of the end effector 102 via a signal line (e.g., copper wire) extending through the cable 120 and through the length of the shaft 116. In other embodiments, the end effector 114 may be communicatively coupled to the nerve monitoring system 108 using other suitable communication means.

[0092] The nerve monitoring system 108 can determine nerve location and activity before therapeutic neuromodulation to determine a precise treatment area corresponding to the location of the desired nerve, determine the effect of therapeutic neuromodulation during treatment, and / or evaluate whether the therapeutic neuromodulation treated the target nerve to the desired extent after treatment. This information can be used to make various determinations related to nerves in close proximity to the target site, such as whether the target site is suitable for neuromodulation. In addition, the nerve monitoring system 108 can also compare the nerve location and / or activity detected before and after therapeutic neuromodulation, and compare the change in nerve activity with a predetermined threshold to assess whether the application of therapeutic neuromodulation to the treatment site is effective. For example, the nerve monitoring system 108 can further determine an electroneurogram (ENG) signal based on a recording of the electrical activity of the neuron obtained by the end effector 114 before and after therapeutic neuromodulation. A statistically significant (e.g., measurable or significant) reduction in the ENG signal obtained after neuromodulation can be used as an indicator that the nerve has been sufficiently ablated. Additional features and functionality of the neuromonitoring system 108, as well as other functionality of the various components of the console 104, are described at least in U.S. Publication No. 2016 / 0331459 and U.S. Publication No. 2018 / 0133460, the contents of each of which are incorporated herein by reference in their entirety.

[0093] As will be described in greater detail herein, the neuromodulation device 102 provides access to a target site deep within the nasal region, such as at the direct entry of parasympathetic nerve fibers into the nasal cavity, to therapeutically modulate autonomic activity within the nasal cavity. In certain embodiments, for example, the neuromodulation device 102 can position the end effector 114 to contact a target site within the nasal cavity associated with postganglionic parasympathetic nerve fibers that innervate the nasal mucosa.

[0094] Figure 3A is a cutaway side view showing the anatomy of the lateral nasal wall, and Figure 3B yes Figure 1A Magnified lateral view of the nerves of the lateral nasal wall. The sphenopalatine foramen (SPF) is an opening or canal defined by the palatine and sphenoid bones through which the sphenopalatine vessels and posterior superior nasal nerve enter the nasal cavity. More specifically, the orbital and sphenoid processes of the vertical plate of the palatine bone define the sphenopalatine notch, which is transformed into the SPF by articulation with the surface of the sphenoid body.

[0095] The location of the SPF varies widely within the posterior region of the lateral nasal cavity, which makes it difficult to visually locate the SPF. Typically, the SPF is located in the middle meatus (MM). However, anatomical variations can also result in the SPF being located in the superior meatus (SM) or at the transition between the superior and middle meatus. For example, in some individuals, the inferior edge of the SPF was measured to be approximately 19 mm above the horizontal plate of the palatine bone (i.e., the nasal sill), which is approximately 13 mm above the horizontal piece of the inferior turbinate (IT), and the average distance from the nasal sill to the SPF was 64.4 mm, resulting in an approach angle of approximately 11.4° from the nasal sill to the SPA. However, due to the wide variation in its location, studies measuring the precise location of the SPF have limited practical application.

[0096] Anatomical variations in the SPF are expected to correspond to changes in the autonomic neural and vascular pathways entering the nasal cavity. In general, the posterior nasal nerve (also known as the posterior superior lateral nasal nerve) branches from the pterygopalatine ganglion (PPG) (also known as the sphenopalatine ganglion), passes through the SPF to enter the lateral nasal wall of the nasal cavity, and the sphenopalatine artery passes through the SPF on the lateral nasal wall from the pterygopalatine fossa. The sphenopalatine artery divides into two main parts: the posterolateral nasal branch and the posterior septal branch. The main branch of the posterolateral nasal artery enters the inferior turbinate IT downward (e.g., between approximately 1.0 mm and 1.5 mm from the posterior tip of the inferior turbinate IT), while another branch enters the middle turbinate MT and branches anteriorly and posteriorly.

[0097] In addition to the SPF, studies have shown that more than 30% of human patients have one or more accessory foramina, which also carry arteries and nerves entering the nasal cavity. The accessory foramina are usually smaller than the SPF and are positioned below the SPF. For example, the posterior nasal artery and the posterior nasal nerve can have one, two, three or more branches, which extend through the corresponding accessory foramina. The variability of the position, size and quantity associated with the accessory foramina and the associated branch arteries and nerves passing through the accessory foramina cause a lot of uncertainty about the position of the vascular system and nerves in the sphenopalatine region. In addition, the natural anatomical structure extending from the SPF usually includes a deep inferior groove and / or superior groove that carries the neural pathway and the arterial pathway, which makes it difficult to locate the arterial branches and the nerve branches. For example, these grooves can extend more than 5mm long, more than 2mm wide and more than 1mm deep, thereby forming a path that is important enough to carry the arteries and nerves. The changes caused by the grooves and accessory foramina in the sphenopalatine region make it extremely difficult for surgeons to locate and touch the arteries and nerves (located behind the arteries).

[0098] Recent microanatomical dissections of the pterygopalatine fossa (PPF) have further demonstrated that the anatomy of the region surrounding the SPF is highly variable, indicating that multiple efferent branches extending from the pterygopalatine ganglion (PPG) innervate the orbital and nasal mucosa through many groups of small nerve fascicles rather than a single postganglionic autonomic nerve (e.g., the posterior nasal nerve). Studies have shown that at least 87% of humans have small holes and microbranches in the palatine bone.

[0099] For example, Figure 3C is an anterior view of the left palatine bone, showing the geometry of the foramina and microbranchs in the left palatine bone. Figure 3C In the figure, the solid areas represent nerves that pass directly through the palatine bone, while the hollow circles represent nerves that are associated with different foramina. Figure 3C It was demonstrated that the medial portion of the palatine bone may include at least 25 accessory posterolateral nerves.

[0100] The respiratory part of the nasal mucosa is composed of a ciliated pseudostratified columnar epithelium with a basement membrane. Nasal secretions (e.g., mucus) are secreted by goblet cells, submucosal glands, and plasma exudates. The nasal submucosal glands and blood vessels are highly regulated by parasympathetic innervation from the pterygoid duct and other nerves. Parasympathetic (cholinergic) stimulation by acetylcholine and vasoactive intestinal peptide usually causes mucus production. Accordingly, parasympathetic innervation of the mucosa is the main cause of submucosal gland activation / overactivation, venous distension (e.g., congestion), and increased blood flow to the nasal lining blood vessels. Accordingly, cutting off or regulating the parasympathetic pathways that innervate the mucosa is expected to reduce or eliminate the overactivation and vascular congestion of the submucosal glands that cause symptoms associated with sinusitis and other indications.

[0101] As described above, the postganglionic parasympathetic nerve fibers that innervate the nasal mucosa (i.e., the posterior superior nasal nerve) are considered to pass only through the SPF as the sphenopalatine neurovascular bundle. The posterior nasal nerve is a branch of the maxillary nerve, innervating the nasal cavity through many smaller medial and lateral branches, which extend through the mucosa of the superior turbinate ST and the middle turbinate MT (i.e., the nasal concha) and reach the nasal septum. The nasopalatine nerve is usually the largest nerve in the medial posterior superior nasal nerve, and the nasopalatine nerve passes forward and downward in the groove on the vomer to reach the bottom of the nasal cavity. From here, the nasopalatine nerve passes through the incisor fossa of the hard palate and is connected with the greater palatine nerve to supply the hard palate mucosa. The posterior superior nasal nerve passes through the pterygopalatine ganglion PPG without synapse, and reaches the maxillary nerve through its ganglion branches.

[0102] Based on the understanding that the posterior nasal nerve only passes through the SPF to innervate the nasal mucosa, surgical procedures have been performed to selectively cut the posterior nasal nerve as it leaves the SPF. However, as discussed above, the parasympathetic sinus pathway actually includes separate branches extending from the pterygopalatine ganglion (PPG) to innervate the nasal mucosa through multiple small nerve bundles (i.e., the posterior lateral accessory nerve) rather than through a single branch extending through the SPF. These branches conduct through multiple fissures, accessory foramina, and foramina throughout the palatine bone and may exhibit anastomotic loops with the SPF and other accessory nerves. Therefore, if only the parasympathetic nerves passing through the SPF are cut, almost all patients (e.g., 90% or more of patients) will retain intact parasympathetic motor fibers on the posterior lateral mucosa, which will result in the persistence of the symptoms that the neurectomy is intended to alleviate.

[0103] Accordingly, embodiments of the present disclosure are configured to therapeutically regulate the presence of Figure 3B The target area T) shown in the figure is a nerve at a precise and focused treatment site corresponding to the location of the branches extending through the fissure, accessory foramen, and foramen. In certain embodiments, the target nerve is a postganglionic parasympathetic nerve that continues to innervate the nasal mucosa. This selective nerve treatment is also expected to reduce the rate of postoperative nasal crusting and dryness because it allows the clinician to titrate the degree of anterior denervation by judiciously leaving the orbitonasal branches. In addition, embodiments of the present disclosure are also expected to maintain at least some sympathetic tone by retaining a portion of the sympathetic contribution of the deep petrosal nerve and the plexus around the internal maxillary artery, thereby resulting in improved outcomes regarding nasal obstruction. Furthermore, embodiments of the present disclosure are configured to target nasal regions directed to multiple parasympathetic nerve entry sites (e.g., accessory foramen, fissure, and foramen) to provide complete resection of all anastomotic loops, thereby reducing long-term reinnervation rates.

[0104] Figure 4is a side view of one embodiment of a handheld device 102 for providing therapeutic nasal nerve modulation consistent with the present disclosure. As shown, the device 102 includes a multi-segment end effector 114, a shaft 116 operably associated with the end effector 114, and a handle 118 operably associated with the shaft 116, the multi-segment end effector being transformable between a retracted configuration and an expanded, deployed configuration. The multi-segment end effector 114 includes at least a first segment 122 and a second segment 124 spaced apart from each other. The first segment 122 is generally positioned closer to the distal end of the shaft 116 and is therefore sometimes referred to herein as the proximal segment 122, while the second segment 124 is generally positioned farther from the distal end of the shaft 116 and is therefore sometimes referred to herein as the distal segment 124. Each of the first segment 122 and the second segment 124 is transformable between a retracted configuration and a deployed configuration, the retracted configuration including a low-profile delivery state that facilitates intraluminal delivery of the end effector 114 to a treatment site within the nasal region, and the deployed configuration including a low-profile delivery state that facilitates intraluminal delivery of the end effector 114 to a treatment site within the nasal region. Figure 4 Shown and FIG. 5A to FIG. 5F The handle 118 includes at least a first mechanism 126 and a second mechanism 128 separate from the first mechanism 124, the first mechanism being used to deploy the multi-segment end effector 114, particularly the first and second segments 122, 124, from a retracted configuration to an expanded configuration, and the second mechanism being used to control the energy output of any one of the first and second segments 122, 124 of the end effector 114, particularly electrodes or other energy elements provided by the first and / or second segments 122, 124. The handheld device 102 may further include an auxiliary line 121, which may provide, for example, a fluid connection between a fluid source and the shaft 116, such that the fluid may be provided to a target site through the distal end of the shaft 116. In some embodiments, the auxiliary line 121 may provide a connection between a vacuum source and the shaft 116, such that the device 102 may include a suction capability (through the distal end of the shaft 116).

[0105] Figure 5A , Figure 5B , Figure 5C , Figure 5D , Figure 5E and Fig. 5F is an enlarged view of the multi-segment end effector 114 showing various views of the first and second segments 122 , 124 in greater detail. Figure 5A It is an enlarged perspective view of the multi-stage end effector 114 . Figure 5B It is an exploded perspective view of the multi-stage end effector 114 . Figure 5C and Figure 5D They are respectively an enlarged top view and a side view of the multi-segment end effector 114 . Figure 5E 1 is an enlarged front (proximally facing) view of the first segment 122 of the multi-segment end effector 114 . Fig. 5F1 is an enlarged front (proximally facing) view of the second segment 124 of the multi-segment end effector 114 .

[0106] As shown, the first segment 122 includes at least a first group of flexible support elements, typically in the form of wires, arranged in a first configuration, and the second segment 124 includes a second group of flexible support elements, also in the form of wires, arranged in a second configuration. The first and second groups of flexible support elements include composite wires having conductive properties and elastic properties. For example, in some embodiments, the composite wire includes a shape memory material, such as Nitinol. The flexible support element may further include a highly lubricious coating that may allow for desired electrical insulation properties as well as a desired low friction surface finish. Each of the first and second segments 122, 124 may be transformed between a retracted configuration and an expanded, deployed configuration, such that in the deployed configuration, the first and second groups of flexible support elements are configured to attach one or more electrodes (see FIG. 1 ) disposed on the respective segments. Figure 5E and Fig. 5F The electrode 136 in is positioned to contact one or more target sites.

[0107] As shown, when in the expanded deployed configuration, the first set of support elements of the first section 122 includes at least a first pair of struts 130a, 130b, a second pair of struts 132a, 132b, the first pair of struts each including a ring (or leaflet) shape and extending in an upward direction, and the second pair of struts each including a ring (or leaflet) shape and extending in a downward direction, generally in an opposite direction relative to at least the first pair of struts 130a, 130b. It should be noted that the terms "upward" and "downward" are used to describe the orientation of the first and second sections 122, 124 relative to each other. More specifically, the first pair of struts 130a, 130b extend obliquely outwardly and spaced apart from each other in a first direction generally relative to the longitudinal axis of the multi-segment end effector 114. Similarly, the second pair of struts 132a, 132b extend obliquely outwardly and spaced apart from each other in a second direction substantially opposite to the first direction relative to the longitudinal axis of the multi-segment end effector.

[0108] The second set of support elements of the second section 124, when in the expanded, deployed configuration, includes a second set of struts 134(1), 134(2), 134(n) (approximately six struts), each strut including an annular shape extending outwardly to form an open-ended circular shape. As shown, the open-ended circular shape is generally similar to a blooming flower, wherein each annular strut 134 can be generally similar to a petal. It should be noted that the second set of struts 134 can include any number of individual struts and is not limited to the six shown. For example, in some embodiments, the second section 124 can include two, three, four, five, six, seven, eight, nine, ten, or more struts 134.

[0109] The first and second sections 122, 124, specifically the pillars 130, 132 and 134 include one or more energy delivery elements, such as multiple electrodes 136. It should be noted that any individual pillar may include any number of electrodes 136 and is not limited to one electrode as shown. In the expanded state, the pillars 130, 132 and 134 can position any number of electrodes 136 against tissue at a target site in the nasal region (e.g., close to the palatine bone below the SPF). The electrode 136 can apply bipolar or multipolar radiofrequency (RF) energy to the target site to therapeutically regulate the postganglionic parasympathetic nerves that innervate the nasal mucosa close to the target site. In various embodiments, the electrode 136 can be configured to apply pulsed RF energy with a desired duty cycle (e.g., 1 second on / 0.5 second off) to regulate the temperature increase in the target tissue.

[0110] The first and second segments 122, 124 and the associated struts 130, 132, and 134 can have sufficient rigidity to support the electrode 136 and position or press the electrode 136 against tissue at the target site. In addition, each expanded first and second segment 122, 124 can press against surrounding anatomical structures proximate to the target site (e.g., nasal concha, palatine bone, etc.), and the individual struts 130, 132, 134 can at least partially conform to the shape of the adjacent anatomical structures to anchor the end effector 114. In addition, the expansion and compliance of the struts 130, 132, 134 can help place the electrode 136 in contact with the surrounding tissue at the target site. The electrode 136 can be made of platinum, iridium, gold, silver, stainless steel, platinum-iridium, cobalt chromium, iridium oxide, polyethylene dioxythiophene (PEDOT), titanium, titanium nitride, carbon, carbon nanotubes, platinum ash, drawn filled tube (DFT) with a silver core, and / or other suitable materials for delivering RF energy to the target tissue. In some embodiments, such as Figure 6 As shown in , the struts can include an outer sheath surrounding the conductive wires, wherein portions of the outer sheath are selectively absent along the length of the struts, thereby exposing the underlying conductive wires to act as energy delivery elements (i.e., electrodes) and / or sensing elements as described in more detail herein.

[0111] In some embodiments, each electrode 136 can be operated independently of the other electrodes 136. For example, each electrode can be activated individually and the polarity and amplitude of each electrode can be selected by an operator or a control algorithm (e.g., executed by the controller 107 previously described herein). Selective independent control of the electrodes 136 allows the end effector 114 to deliver RF energy to highly customized areas. For example, a selected portion of the electrodes 136 can be activated to target nerve fibers in a specific area, while other electrodes 136 remain inactive. In some embodiments, for example, the electrodes 136 can be activated on a portion of the second segment 124 adjacent to the tissue at the target site, and the electrodes 136 that are not proximate to the target tissue can remain inactive to avoid applying energy to non-target tissue. Such a configuration facilitates selective therapeutic modulation of the nerves on the lateral nasal wall within one nostril without applying energy to structures in other parts of the nasal cavity.

[0112] The electrodes 136 are electrically coupled to an RF generator (e.g., the generator 106 of FIG. 1 ) via a wire (not shown) extending from the electrodes 136 through the shaft 116 and to the RF generator. When each electrode 136 is independently controlled, each electrode 136 is coupled to a corresponding wire extending through the shaft 116. In other embodiments, multiple electrodes 116 may be controlled together, so that multiple electrodes 116 may be electrically coupled to the same wire extending through the shaft 116. As previously described, the RF generator and / or a component operably coupled thereto (e.g., a control module) may include a customized algorithm for controlling the activation of the electrodes 136. For example, the RF generator may deliver RF power of approximately 460-480 kHz (+ or -5 kHz) to the electrodes 136, and while doing so, activate the electrodes 136 in a predetermined pattern selected based on the position of the end effector 114 relative to the treatment site and / or the identified location of the target nerve. The RF generator is capable of providing bipolar low power (10 Watts, with a maximum setting of 50 Watts) RF energy delivery and further provides multiplexing capabilities (across up to 30 channels).

[0113] Once deployed, the first and second segments 122, 124 contact and conform to the shape of the corresponding location, including the shape that conforms to and complements the one or more anatomical structures at the corresponding location. In turn, the first and second segments 122, 124 are accurately positioned within the nasal cavity to subsequently apply RF thermal energy to one or more target sites in a precise and focused manner through one or more electrodes 136 to therapeutically modulate associated neural structures. More specifically, the shape and size of the first and second segments 122, 124 when in the expanded configuration are specifically designed to place portions of the first and second segments 122, 124 and, therefore, the one or more electrodes 136 associated therewith, in contact with a target site within the nasal cavity associated with postganglionic parasympathetic nerve fibers that innervate the nasal mucosa.

[0114] For example, when the first segment 122 is in the expanded configuration, the first set of flexible support elements of the first segment 122 conforms to and complements the shape of a first anatomical structure at a first location, and when the second segment is in the expanded configuration, the second set of flexible support elements of the second segment 124 conforms to and complements the shape of a second anatomical structure at a second location. The first and second anatomical structures may include, but are not limited to, the inferior turbinate, the middle turbinate, the superior turbinate, the inferior meatus, the middle meatus, the superior meatus, the pterygopalatine region, the pterygopalatine fossa, the sphenopalatine foramen, the parasphenopalatine foramen, and the sphenopalatine microforamen.

[0115] In some embodiments, the first segment 122 of the multi-segment end effector 114 is configured in an expanded configuration to fit around at least a portion of the middle turbinate in an anterior position relative to the middle turbinate, and the second segment 124 of the multi-segment end effector is configured in an expanded configuration to contact multiple tissue locations in the cavity in a posterior position relative to the middle turbinate.

[0116] For example, when the first segment 122 is in the expanded configuration, the first set of flexible support elements (i.e., struts 130 and 132) of the first segment conform to and complement the shape of the lateral attachment and the posterior lower edge of the middle turbinate, and when the second segment 124 is in the expanded configuration, the second set of flexible support elements (i.e., struts 134) of the second segment 124 contact multiple tissue locations in the cavity at a posterior position relative to the lateral attachment and the posterior lower edge of the middle turbinate. Accordingly, when in the expanded configuration, the first and second segments 122, 124 are configured to position one or more associated electrodes 136 at one or more target sites relative to the middle turbinate and any of the multiple tissue locations in the cavity behind the middle turbinate. In turn, the electrodes 136 are configured to deliver RF energy at a level sufficient to therapeutically modulate the postganglionic parasympathetic nerves that innervate the nasal mucosa at the innervation pathways within the patient's nasal cavity.

[0117] like Figure 5EAs shown in , the first section 122 includes a bilateral geometry. In particular, the first section 122 includes two identical sides, including a first side formed by pillars 130a, 132a and a second side formed by pillars 130b, 132b. When the first section 122 is in an expanded state, this bilateral geometry allows at least one of the two sides to conform to and adapt to the anatomical structure in the nasal cavity. For example, when in an expanded state, multiple pillars 130a, 132a contact multiple locations along multiple parts of the anatomical structure, and the electrodes provided by the pillars are configured to emit energy at a level sufficient to form multiple micro-lesions in the tissue to mucus production and / or mucosal congestion elements, which interrupt neural signals. In particular, when the first section 122 is in an expanded configuration, the pillars 130a, 132a conform to and complement the shape of the lateral attachment and the posterior lower edge of the middle turbinate, thereby allowing both sides of the anatomical structure to receive energy from the electrodes. By having this independence between the first side and the second side (i.e., the right side and the left side) configuration, the first section 122 is a true bilateral device. By providing a bilateral geometry, the multi-segment end effector 114 does not need to reuse a configuration to treat the other side of the anatomical structure because both sides of the structure are taken into account simultaneously due to the bilateral geometry. The microlesion pattern produced can be repeatable and predictable in both macro elements (depth, volume, shape parameters, surface area) as well as micro elements (the threshold of action within the scope of the macro envelope can be controlled), as will be described in more detail herein. The system of the present invention is further capable of establishing gradients within allowing for control of neural action without widespread effects on other cell bodies, as will be described in more detail herein.

[0118] Figure 7 is along Figure 47-7 of the handheld device. As shown, the shaft 116 can be constructed by multiple parts to have the ability to constrain the end effector 114 to a retracted configuration (i.e., a low-profile delivery state) when the end effector 114 is retracted into the shaft 116 and further provide a non-destructive, low-profile and durable way for delivering the end effector 114 to the target site. The shaft 116 includes a coaxial tube that travels from the handle 118 to the distal end of the shaft 116. The shaft 116 assembly is low-profile to ensure transnasal delivery treatment. The shaft 116 includes an outer sheath 138 around the hypotube 140, which is further assembled on the electrode wire 129 around the inner cavity 142. The outer sheath 138 is used as an interface between the anatomical structure and the device 102. The outer sheath 138 can generally include a low-friction PTFE liner to minimize the friction between the outer sheath 138 and the hypotube 140 during deployment and retraction. In particular, the outer sheath 138 may generally include an encapsulating braid along the length of the shaft 116 to provide flexibility while maintaining kink resistance and further maintaining column and / or tensile strength. For example, the outer sheath 138 may include a soft Pebax material that is atraumatic and capable of being smoothly delivered through the nasal passage. The outer sheath 138 may further include orientation / landmark markings on its outer surface, typically at the distal end, wherein these markings may provide an operator with a visual indication of the architecture and / or spatial orientation of the first and / or second segments 122, 124 of the end effector 114 to assist in positioning and deployment of the end effector 114.

[0119] The hypotube 140 is assembled on the electrode wire, starting from the handle 118 and traveling to the proximal end of the end effector 114. The hypotube 140 is generally used to protect the wire during delivery and has ductility to achieve flexibility without kinking, thereby improving traceability. The hypotube 140 provides rigidity and allows the device 102 to be twistable to ensure that the end effector 114 is accurately placed. The hypotube 140 also provides a low friction outer surface that can achieve small forces when the outer sheath 138 moves relative to the hypotube 140 during deployment and retraction or restraint. The shaft 116 can be pre-formed in a manner that complements the nasal cavity. For example, the hypotube 140 can be annealed to produce a curved shaft 116 with a preset curve. The hypotube 140 can include, for example, a stainless steel tube that is connected to a liner in the outer sheath 138 for low friction movement.

[0120] The lumen 142 may generally provide a channel for fluid extraction during a treatment procedure. For example, the lumen 142 extends from the distal end of the shaft 116 through the hypotube 140 and through the fluid line ( Figure 4 The inner cavity 142 material is selected to resist the forces of the external components acting thereon during surgery.

[0121] Figure 8 is a side view of the handle 118 . Fig. 9 1 is a side view of the handle 118 showing the internal components enclosed therein. The handle 118 generally includes an ergonomically designed grip portion that provides ambidextrous use for both left-handed and right-handed use and conforms to the anthropometrics of the hand to allow at least one of a forehand grip and a backhand grip during use in surgery. For example, the handle 118 may include a specific profile, including recesses 144, 146, and 148, which are designed to naturally receive one or more fingers of the operator in a forehand grip or a backhand grip and provide a comfortable feel for the operator. For example, in a backhand grip, recess 144 may naturally receive the operator's index finger, recess 146 may naturally receive the operator's middle finger, and recess 148 may naturally receive the operator's ring finger and pinky (little finger or pinky finger) around the proximal protrusion 150, and the operator's thumb naturally rests on the top of the handle 118 adjacent to the first mechanism 126. In a forehand grip, the operator's index finger can naturally rest on the top of the handle 118 adjacent to the first mechanism 126, while the recess 144 can naturally receive the operator's middle finger, the recess 146 can naturally receive a portion of the operator's middle finger and / or ring finger, and the recess 148 can naturally receive the operator's thumb and index finger and rest in the space between the operator's thumb and index finger (sometimes referred to as the purlicue).

[0122] As previously described, the handle includes a plurality of user-operated mechanisms, including at least a first mechanism 126 for deploying the end effector 114 from a retracted configuration to an extended deployed configuration, and a second mechanism 128 for controlling the energy output of the end effector, in particular, controlling the energy delivery from one or more electrodes 136. As shown, the user inputs for the first and second mechanisms 126, 128 are positioned at a distance from each other sufficient to allow simultaneous single-handed operation of the two user inputs during surgery. For example, the user input of the first mechanism 126 is positioned at the top portion of the handle 118 adjacent to the grip portion, while the user input of the second mechanism 128 is positioned at the side of the handle 118 adjacent to the grip portion. Thus, in a reverse-hand grip, the operator's thumb rests on the top portion of the handle adjacent to the first mechanism 126, and at least their middle finger is positioned adjacent to the second mechanism 128, and each of the first and second mechanisms 126, 128 is accessible and can be actuated. In the forehand grip system, the operator's index finger rests on the top portion of the handle adjacent to the first mechanism 126, and at least their thumb is positioned adjacent to the second mechanism 128, each of the first and second mechanisms 126, 128 being accessible and capable of being actuated. Accordingly, the handle accommodates a variety of grip styles and provides a degree of comfort to the surgeon, further improving the execution and overall outcome of the procedure.

[0123] Reference Fig. 9, showing various components disposed within the handle 118. As shown, the first mechanism 126 can generally include a rack and pinion assembly that provides movement of the end effector 114 between a retracted configuration and an expanded configuration in response to input from a user-operated controller. The rack and pinion assembly generally includes a set of gears 152 for receiving input from the user-operated controller and converting the input into a linear motion of a rack member 154 that is operably associated with at least one of the shaft 116 and the end effector 114. The rack and pinion assembly includes a gear ratio sufficient to balance the stroke length and the retraction and deployment forces, thereby improving control over the deployment of the end effector. As shown, for example, the rack member 154 can be coupled to a portion of the shaft 116 so that movement of the rack member 154 in a direction toward the proximal end of the handle 118 causes a corresponding movement of the shaft 116 while the end effector 114 remains fixed, thereby exposing the end effector 114 and allowing the end effector 114 to transition from a constrained retracted configuration to an extended deployed configuration. Similarly, when the rack member 154 moves in a direction toward the distal end of the handle 118, a corresponding movement of the shaft 116 is caused while the end effector 114 remains fixed, thereby enclosing the end effector 114 within the shaft 116. It should be noted that in other embodiments, the rack member 154 can be directly coupled to a portion of the end effector 114, so that movement of the rack member 154 causes a corresponding movement of the end effector 114 while the shaft 116 remains fixed, thereby transitioning the end effector 114 between the retracted configuration and the deployed configuration.

[0124] The user-operated controller associated with the first mechanism 126 may include a slider mechanism operably associated with the rack and pinion track assembly. Movement of the slider mechanism in a rearward direction toward the proximal end of the handle causes the end effector 114 to transition to the deployed configuration, and movement of the slider mechanism in a forward direction toward the distal end of the handle causes the end effector to transition to the retracted configuration. In other embodiments, the user-operated controller associated with the first mechanism 126 may include a roller mechanism operably associated with the rack and pinion track assembly. Rotation of the wheel in a rearward direction toward the proximal end of the handle causes the end effector to transition to the deployed configuration, and rotation of the wheel in a forward direction toward the distal end of the handle causes the end effector to transition to the retracted configuration.

[0125] The user-operated controller associated with the first mechanism 126 can generally provide high-precision control over the deployment (and retraction) of the first and second segments 122, 124. For example, in some cases, the operator may want to deploy only the second segment 124 during surgery, while the first segment 122 remains in the retracted configuration. The user-operated controller allows the operator to provide a sufficient degree of input (i.e., sliding a slider mechanism or rolling a roller to a particular position) that causes only the second segment 124 to transition from the retracted configuration to the deployed configuration (while the first segment 122 remains enclosed within the shaft 116 and in the retracted configuration). For example, in some embodiments, the end effector 114 can further include a detent feature, such as a snap or similar element, positioned between the first and second segments 122, 124 and configured to provide feedback to the surgeon, such as tactile or haptic feedback, during deployment of the end effector segments to alert the surgeon when at least the second segment 124 is fully deployed. In particular, when the surgeon slides the slider mechanism or rolls the roller during deployment of the second segment 124, the detent feature (disposed between the first and second segments 122, 124) can then reach a portion of the shaft 116 and cause an increase in resistance on the slider mechanism or roller, thereby indicating to the surgeon that the second segment 124 has been deployed and the first segment 122 remains in the retracted configuration. Therefore, the surgeon can position and orient the second segment 124 as they desire without having to worry about the first segment 122 because it remains in the retracted configuration. In turn, once the second segment 124 is positioned at the desired target site, the surgeon can then deploy the first segment 122 to perform the procedure. However, in some cases, only the second segment 124 can be used to perform the procedure (i.e., deliver energy to one or more target sites in contact with the second segment 124), and as such, the first segment 122 may never be deployed.

[0126] The second mechanism 128 can generally include a user-operated controller configured to be actuated between at least an active position and an inactive position to control energy delivery from the end effector 114, particularly energy delivery from the electrode 136. The user-operated controller can be multi-mode in that the user-operated controller can be actuated between multiple positions that provide different functions / modes. For example, based on a single user input (i.e., a single press of an associated button within the controller), the second mechanism can provide a baseline juxtaposition / sensing check function before adjustment. After pressing and holding the controller button for a predefined period of time, the energy output from the end effector can be activated. Further, after double-clicking the controller button, the energy output is stopped.

[0127] Additionally, the handle and / or shaft may include markings that provide the surgeon with the spatial orientation of the end effector when the end effector is in the nasal cavity. Fig.10is a side view of the handle 118 showing a plurality of markings on the distal end of the handle 118, and Fig.11 is a perspective view of a portion of the shaft 116 showing a plurality of markings on the distal end thereof. In particular, a plurality of markings can be disposed on the handle and / or the shaft and provide a visual indication of the spatial orientation of one or more portions of the first and second segments of the end effector when in the deployed configuration. The markings can include, for example, text, symbols, color-coded indicia, etc. Thus, during initial placement of the end effector, when in the retracted configuration and enclosed within the shaft, the surgeon can rely on the markings on the handle and / or the shaft as a visual indication of the spatial orientation of the end effector (e.g., linear, axial, and / or depth position), thereby ensuring that once deployed, the end effector, including both the first and second segments, is positioned at the intended location within the nasal cavity.

[0128] For example, the handle and / or shaft may include markings associated with each of the first pair of struts 130a, 130b and each of the second pair of struts 132a, 132b to provide an operator with a visual indication of the resulting spatial orientation and configuration of at least the first segment 122 when initially navigating within the nasal cavity and delivering the distal end of the shaft 116 to the target site prior to deploying the end effector 114. In other words, the markings provide the operator with an indication of the orientation of at least the first segment 122 of the end effector 114 prior to deploying the end effector 114, thereby ensuring accurate positioning at the desired location.

[0129] Fig.12 1 is a partial cutaway side view showing a method for delivering an end effector 114 to a target site in the nasal region according to an embodiment of the present disclosure. As shown, the distal portion of the shaft 116 extends into the nasal meatus NP, passes through the inferior nasal meatus IM between the inferior turbinate IT and the bridge of the nose NS, and extends around the end effector 114 to extend over the posterior portion of the inferior turbinate IT at the treatment site. The treatment site can be positioned proximate to one or more entry points where postganglionic parasympathetic nerves (e.g., branches of the posterior nasal nerve and / or other parasympathetic nerve fibers that innervate the nasal mucosa) enter the nasal cavity. In other embodiments, the target site can be at other locations within the nasal cavity, depending on the location of the target nerve.

[0130] In various embodiments, the distal portion of the shaft 116 can be guided into position at the target site by a guidewire (not shown) using an over the wire (OTW) or rapid exchange (RX) technique. For example, the end effector 114 can include a channel for engaging the guidewire. The intraluminal delivery of the end effector 114 can include inserting the guidewire into an orifice communicating with a nasal cavity (e.g., a nasal passage or a mouth), and moving the shaft 116 and / or the end effector 114 along the guidewire until the end effector 114 reaches the target site (e.g., below the SPF).

[0131] However, in further embodiments, the neuromodulator 102 can be configured for delivery through a guide catheter or guide sheath (not shown) with or without the use of a guide wire. The guide sheath can first be inserted into the lumen into the target site in the nasal region, and then the distal portion of the shaft 116 can be inserted through the guide sheath. At the target site, the end effector 114 can be deployed through the distal opening of the guide sheath or the side port of the guide sheath. In some embodiments, the guide sheath can include a straight portion and a preformed portion with a fixed curve (e.g., a 5mm curve, a 4mm curve, a 3mm curve, etc.), which can be deployed in the lumen to reach the target site. In this embodiment, the guide sheath can have a side port close to or along the preformed curved portion, and the end effector 114 can be deployed through the side port. In other embodiments, the guide sheath can be made of a rigid material, such as a metal material coated with an insulating or dielectric material. In this embodiment, the guide sheath can be substantially straight and used to pass, for example, through the middle nasal meatus MM ( Figure 3A ) through a substantially straight passage to deliver the end effector 114 to the target site.

[0132] Image guidance can be used to help the surgeon position and manipulate the distal portion of the shaft 116, as well as deploy and manipulate the end effector 114, specifically the first and second segments 122 thereof. For example, the endoscope 100 and / or other visualization devices can be positioned to visualize the target site, the positioning of the end effector 114 to the target site, and / or the end effector 114 during therapeutic neuromodulation. The endoscope 100 can be delivered proximate to the target site by extending through the nasal meatus NP and through the middle meatus MM between the inferior turbinate IT and the middle turbinate MT. From a visualized position within the middle meatus MM, the endoscope 100 can be used to visualize the treatment site, the surrounding area of ​​the nasal anatomy, and the end effector 114.

[0133] In some embodiments, the distal portion of the shaft 116 can be delivered through a working channel extending through an endoscope so that the endoscope can provide direct online visualization of the target site and the end effector 114. In other embodiments, the endoscope is combined with the end effector 114 and / or the distal portion of the shaft 116 to provide online visualization of the end effector 114 and / or surrounding nasal anatomical structures. In other embodiments, image guidance can be provided by various other guidance modes, such as image filtering in the infrared (IR) spectrum to visualize the vasculature and / or other anatomical structures, computed tomography (CT), fluoroscopy, ultrasound, optical coherence tomography (OCT), and / or combinations thereof. However, in some embodiments, the image guidance component can be integrated with the neuromodulation device 102 to provide image guidance during positioning of the end effector 114.

[0134] Once positioned at the target site, therapeutic modulation can be applied to a precise localized tissue region via one or more electrodes 136 and / or other features of the end effector 114 to induce one or more desired therapeutic neuromodulatory effects to disrupt parasympathetic motor sensory function. The end effector 114 can selectively target postganglionic parasympathetic nerve fibers innervating the nasal mucosa at a target or treatment site proximal to or entering the nasal region. For example, the end effector 114 can be positioned at least proximal to the SPF ( Figure 3A ) applies therapeutic neuromodulation to therapeutically modulate nerves entering the nasal area through the SPF. The end effector 114 can also be positioned below the SPF to apply therapeutic neuromodulation energy on the accessory foramina and microforamina (e.g., in the palatine bone) through which the smaller medial and lateral branches of the posterior superior lateral nasal nerve enter the nasal area. Purposefully applying energy to the target site can achieve therapeutic neuromodulation along all or at least a portion of the posterior nasal nerve fibers entering the nasal area. The therapeutic neuromodulation effect is generally at least in part a function of power, time, and contact between the energy delivery element and the adjacent tissue. For example, in some embodiments, therapeutic neuromodulation of autonomic nerve fibers is performed by applying RF energy at a power of about 2-20 W (e.g., 5 W, 7 W, 10 W, etc.) for about 1-20 seconds (e.g., 5-10 seconds, 8-10 seconds, 10-12 seconds, etc.).

[0135] Therapeutic neuromodulatory effects may include partial or complete denervation by thermal ablation and / or non-ablative thermal alteration or damage (e.g., by continuous heating and / or resistive heating). The desired thermal heating effect may include raising the temperature of the target nerve fibers above a desired threshold to achieve non-ablative thermal alteration, or above a higher temperature to achieve ablative thermal alteration. For example, the target temperature may be above body temperature (e.g., approximately 37°C) but below approximately 90°C, (e.g., 70-75°C) for non-ablative thermal alteration, or the target temperature may be approximately 100°C, or higher (e.g., 110°C, 120°C, etc.) for ablative thermal alteration. The desired non-thermal neuromodulatory effect may include altering electrical signals transmitted in the nerve.

[0136] It is expected that adequate modulation of at least a portion of the parasympathetic nerves will slow or possibly block autonomic nerve signaling to the nasal mucosa to produce a long-lasting or permanent reduction in nasal parasympathetic nerve activity. It is expected that this will reduce or eliminate activation or overactivation of the submucosal glands and venous congestion, thereby reducing or eliminating the symptoms of rhinosinusitis. Further, because the device 102 applies therapeutic neuromodulation to multiple branches of the posterior nasal nerve, rather than to a single large branch of the posterior nasal nerve branches that enter the nasal cavity at the SPF, the device 102 provides a more complete destruction of the parasympathetic nerve pathways that affect the nasal mucosa and cause sinusitis. Accordingly, it is expected that the device 102 has an enhanced therapeutic effect for treating rhinosinusitis and reduces reinnervation of the treated mucosa.

[0137] In other embodiments, the device 102 can be configured to therapeutically modulate nerves and / or other structures to treat different indications. For example, the device 102 can be used to therapeutically modulate nerves that innervate the paranasal sinuses to treat chronic sinusitis. In further embodiments, the system 100 and device 102 disclosed herein can be configured to therapeutically modulate the vasculature within the nasal anatomy to treat other indications, such as epistaxis (i.e., excessive bleeding from the nose). For example, the system 100 and device 102 described herein can be used to apply therapeutically effective energy to arteries (e.g., the sphenopalatine artery and its branches) as they enter the nasal cavity (e.g., through the SPF, accessory foramen, etc.) to partially or completely coagulate or ligate the artery. In other embodiments, the system 100 and device 102 can be configured to partially or completely coagulate or ligate veins and / or other blood vessels. For such embodiments where the end effector 114 ligates or coagulates vasculature, the system 100 and device 102 would be modified to deliver energy at significantly higher powers (e.g., approximately 100 W) and / or for longer times than required for therapeutic neuromodulation (e.g., 1 minute or more).

[0138] Fig.134 is a flow chart illustrating one embodiment of a method 400 for treating a condition in a nasal cavity of a patient. The method 400 includes advancing a multi-segment end effector in a nasal cavity of a patient (operation 410), wherein the multi-segment end effector includes a first segment spaced apart from a second segment. The multi-segment end effector is retractable and expandable such that once delivered to one or more target sites in the nasal cavity, the first segment and the second segment can be expanded to a specific shape and / or size corresponding to the anatomical structures associated with the nasal cavity and the target sites. The method 400 further includes deploying the first segment and the second segment at respective first and second locations in the nasal cavity (operation 420). In particular, when in the deployed configuration, each of the first and second flexible segments includes a specific geometric shape to complement the anatomical structure of the respective location in the nasal cavity. Accordingly, once deployed, the first segment and the second segment contact and conform to the shape of the respective location, including conforming to and complementing the shape of one or more anatomical structures at the respective location. The method 400 further includes delivering energy to tissue of one or more target sites relative to the first location and the second location through the first segment and the second segment (operation 430). In particular, the first and second segments are accurately positioned within the nasal cavity to subsequently apply RF thermal energy to one or more target sites in a precise and focused manner through one or more electrodes to therapeutically modulate associated neural structures. The shape and size of the first and second segments when in the expanded configuration are specifically designed to place a portion of the first and second segments, and therefore one or more electrodes associated therewith, in contact with a target site within the nasal cavity associated with postganglionic parasympathetic nerve fibers that innervate the nasal mucosa.

[0139] Fig.14 is a flow chart illustrating another embodiment of a method 500 for treating a condition within a nasal cavity of a patient. The method 500 includes providing a treatment device including an end effector transformable between a retracted configuration and an expanded deployed configuration, a shaft operably associated with the end effector, and a handle operably associated with the shaft (operation 510). The method 500 further includes advancing the end effector to one or more target sites within the nasal cavity of the patient (operation 520). The shaft may include a predefined shape (i.e., bent or angled in a particular orientation) to assist in the operation of placing the end effector at the target site. The handle includes an ergonomically designed grip portion that provides ambidextrous use for left-handed and right-handed use and conforms to the anthropometrics of the hand to allow at least one of an overhand grip and an underhand grip during use in a procedure.

[0140] The handle and / or shaft may include markings (e.g., text, symbols, color-coded indicia, etc.) that provide the surgeon with the spatial orientation of the end effector while the end effector is in the nasal cavity. In particular, a plurality of markings may be disposed on the handle and / or shaft and provide a visual indication of the spatial orientation of one or more portions of the first and second segments of the end effector when in the deployed configuration. Thus, during initial placement of the end effector, when in the retracted configuration and enclosed within the shaft, the surgeon may rely on the markings on the handle and / or shaft as a visual indication of the spatial orientation of the end effector (e.g., linear, axial, and / or depth position), thereby ensuring that once deployed, the end effector, including both the first and second segments, is positioned at the intended location within the nasal cavity.

[0141] Method 500 further includes deploying the end effector at one or more target sites (operation 530) and delivering energy from the end effector to tissue at the one or more target sites (operation 540). The handle includes a plurality of user-operated mechanisms, including at least a first mechanism for deploying the end effector from a retracted configuration to an extended deployed configuration and a second mechanism for controlling the energy output of the end effector. The user inputs of the first and second mechanisms are positioned sufficiently far from each other to allow simultaneous single-handed operation of both user inputs during surgery. Accordingly, the handle accommodates a variety of grip styles and provides a degree of comfort to the surgeon, thereby further improving the execution and overall outcome of the surgery.

[0142] Fig.15 6 is a flow chart illustrating another embodiment of a method 600 for treating a condition within a nasal cavity of a patient. The method 600 includes providing a treatment device including a multi-segment end effector including a proximal segment spaced apart from a distal segment and a visual marker (operation 610). As previously described herein, the visual marker can be provided by, for example, a shaft operably associated with the multi-segment end effector. The visual marker can be in the form of text, a symbol, a color-coded indicia, etc., and the visual marker generally provides a user (i.e., a surgeon or other medical professional) with a visual indication of the spatial orientation of one or more portions of the proximal segment when the multi-segment end effector is in the nasal cavity.

[0143] Method 600 further includes advancing the proximal and distal segments through the patient's nasal cavity and past the middle turbinate under image guidance (operation 620) and deploying the distal segment from the retracted configuration to the expanded configuration (operation 630). The image guidance may be in the form of an endoscope and / or other visualization device that may be positioned to provide visualization of one or more locations within the nasal cavity to a user and further provide visualization of the multi-segment end effector and other portions of the treatment device (i.e., at least the distal portion of the shaft having visual markers) during advancement into the nasal cavity to assist the user in placing the multi-segment end effector.

[0144] When the distal segment is deployed to the expanded configuration, method 600 further includes aligning the proximal segment relative to the middle turbinate under image guidance and with reference to the visual marker (operation 640). For example, the visual marker can be disposed on the shaft and provide a visual indication of the spatial orientation of one or more portions of the proximal segment when in the deployed configuration. For example, the deployed proximal segment can include a geometric shape for complementing the shape of the middle turbinate. More specifically, the proximal segment can include a set of flexible support elements that conform to and complement the shape of the middle turbinate when the proximal segment is in the expanded deployed configuration. The visual marker provided by the shaft provides a visual indication of the spatial orientation of one or more portions of the proximal segment, including, for example, the spatial orientation of the set of flexible support elements when in the expanded deployed configuration. Accordingly, aligning the proximal segment relative to the middle turbinate includes a user positioning the shaft and associated visual marker relative to the middle turbinate under image guidance.

[0145] Thus, during initial placement of at least the proximal segment in a retracted configuration, the surgeon can rely on markings on the shaft as a visual indication of the spatial orientation (e.g., linear, axial, and / or depth position) of one or more portions of the proximal segment prior to deployment of the proximal segment, thereby ensuring that the proximal segment is positioned at the intended location within the nasal cavity once deployed.

[0146] Method 600 further includes deploying the proximal segment around the middle turbinate and advancing the deployed proximal segment toward the middle turbinate to establish contact and secure the proximal segment to the middle turbinate (operation 650). Likewise, when the proximal segment is in the expanded deployed configuration, the set of flexible support elements of the proximal segment can conform to and complement the shape of the middle turbinate, thereby ensuring that the deployed proximal segment is secured to the middle turbinate.

[0147] It should be noted that the treatment device further includes a handle operably associated with the multi-segment end effector and the shaft. The handle typically includes a controller mechanism for providing independent, controlled deployment of each of the proximal segment and the distal segment from a retracted configuration to an expanded configuration within the nasal cavity. In particular, in some embodiments, the controller mechanism includes a rack and pinion assembly that provides movement of at least one of the proximal segment and the distal segment between the retracted configuration and the expanded configuration in response to user input from an associated user-operated controller. The rack and pinion assembly may include, for example, a set of gears that are used to receive user input from the user-operated controller and convert the user input into linear movement of a rack member operably associated with the multi-segment end effector.

[0148] The controller mechanism may further include a detent feature positioned relative to the proximal segment and the distal segment and configured to provide a user with effective feedback indicating the deployment of at least one of the proximal segment and the distal segment. The effective feedback may be in the form of tactile feedback provided by the controller mechanism. For example, for the corresponding movement of at least one of the proximal segment and the distal segment between the retracted configuration and the extended configuration and / or the configuration between them (i.e., multiple configurations between the fully retracted configuration and the fully extended configuration), the tactile feedback may include an increase or decrease in resistance associated with the user input of the controller mechanism. For example, after the distal segment is deployed, due to the interaction with the detent, the controller mechanism may provide the user with tactile feedback in the form of vibration or other movement (e.g., click or resistance change) through a user-operated controller. The tactile feedback may indicate to the user that the distal segment is fully deployed and any further input of the user-operated controller will cause the deployment of the proximal segment. The controller mechanism may further provide specific tactile feedback during the deployment of a given segment, such as the deployment of the proximal segment. For example, the tactile feedback may be in the form of an increase or decrease in resistance on a user-operated control, corresponding, for example, to the extent to which the proximal segment is deployed.

[0149] In some embodiments, the controller mechanism may further include a friction-based feature configured to provide stable movement of at least one of the proximal segment and the distal segment between the retracted configuration and the expanded configuration, and further provide effective feedback to the user indicating the deployment of at least one of the proximal segment and the distal segment. For example, the friction-based feature may include a locking mechanism configured to provide constant friction between one or more portions of the rack and pinion assembly, the friction being sufficient to maintain the position of at least one of the proximal segment and the distal segment during deployment thereof.

[0150] For example, whether or not the user maintains contact with the user-operated controller, constant friction can be sufficient to keep any of the proximal or distal segments in a certain position when the segment is transformed between the retracted configuration and the expanded configuration. In other words, the user does not need to maintain contact with the user-operated controller to ensure that the proximal or distal segments remain in a certain position during their deployment. Instead, the user can only interact with the user-operated controller to transform one of the proximal and distal segments into a desired configuration, and the constant friction provided by the locking mechanism is sufficient to maintain the configuration of the proximal or distal segments when the user's hand is released (i.e., removing any contact with the user-operated controller). The level of constant friction is sufficient to prevent undesirable movement (i.e., unintentional folding or expansion) of the proximal or distal segments, while still allowing the user to overcome this friction to move the proximal or distal segments to the desired configuration according to the user input of the user-operated controller.

[0151] In some embodiments, the user-operated controller includes a slider mechanism operably associated with the rack and pinion track assembly, wherein movement of the slider mechanism in a first direction causes at least one of the proximal segment and the distal segment to transition to an extended configuration, and movement of the slider mechanism in a second, opposite direction causes at least one of the proximal segment and the distal segment to transition to a retracted configuration. In other embodiments, the user-operated controller includes a roller mechanism operably associated with the rack and pinion track assembly, wherein rotation of the wheel in a first direction causes at least one of the proximal segment and the distal segment to transition to an extended configuration, and rotation of the wheel in a second, opposite direction causes at least one of the proximal segment and the distal segment to transition to a retracted configuration. Thus, during deployment of the proximal segment, the slider mechanism or roller can provide increased resistance to the user as the user transitions the proximal segment from a fully retracted configuration to a fully deployed configuration.

[0152] Accordingly, during deployment of either the distal segment or the proximal segment, the controller mechanism provides effective feedback to the user, wherein such effective feedback may indicate which segment is being effectively controlled and / or the degree of deployment of either the distal segment or the proximal segment, thereby improving the user's control over the deployment of either the distal segment or the proximal segment.

[0153] After the proximal segment is fixed to the middle turbinate, the method 600 further includes delivering energy to the middle turbinate through the proximal segment to treat the condition (operation 660). The condition may include, but is not limited to, allergic rhinitis, non-allergic rhinitis, chronic rhinitis, acute rhinitis, chronic sinusitis, acute sinusitis, chronic rhinosinusitis, acute rhinosinusitis, and drug-resistant rhinitis, and combinations thereof. In some embodiments, delivering energy from the proximal segment includes delivering radiofrequency (RF) energy to the middle turbinate tissue at one or more target sites through one or more electrodes provided by the proximal segment, wherein the one or more target sites are associated with parasympathetic innervation. In some embodiments, the RF energy is delivered through the one or more electrodes provided by the proximal segment to a level sufficient to therapeutically modulate the postganglionic parasympathetic nerves that innervate the nasal mucosa at the innervation pathways within the patient's nasal cavity.

[0154] Thus, the handheld device of the present invention provides a user-friendly, non-invasive treatment modality for rhinosinusitis conditions, including the precise and focused application of RF thermal energy to a desired target site to therapeutically modulate the desired neural structure without causing collateral accidental damage or destruction to other neural structures. Thus, the efficacy of a vidian neurectomy procedure can be achieved using the system and method of the present invention without the disadvantages discussed above. Most notably, the handheld device provides surgeons with a user-friendly, non-invasive, and precise method for treating runny nose and other symptoms of rhinosinusitis by targeting only those specific neural structures associated with such conditions, particularly the postganglionic parasympathetic nerves innervating the nasal mucosa, thereby disrupting the parasympathetic innervation and interrupting the parasympathetic tone. Accordingly, such treatment effectively treats rhinosinusitis conditions while greatly reducing the risk of lateral damage or destruction to other neural fibers, thereby reducing the likelihood of unexpected complications and side effects.

[0155] Neuromodulation monitoring, feedback and mapping capabilities

[0156] As previously described, the system 100 includes a console 104 to which the device 102 is connected. The console 104 is configured to provide various functions for the neuromodulation device 102, which may include, but are not limited to, controlling, monitoring, supplying, and / or otherwise supporting the operation of the neuromodulation device 102. The console 104 may be further configured to generate energy of a selected form and / or magnitude for delivery to tissue or nerves at a target site via the end effector 114, and thus the console 104 may have different configurations depending on the treatment mode of the device 102. For example, when the device 102 is configured for electrode-based, thermal element-based, or transducer-based treatment, the console 104 may include an energy generator 106 configured to generate RF energy (e.g., monopolar, bipolar, or multipolar RF energy), pulsed electrical energy, microwave energy, light energy, ultrasound energy (e.g., intravascularly delivered ultrasound and / or HIFU), direct thermal energy, radiation (e.g., infrared, visible light, and / or gamma radiation), and / or another suitable type of energy. When the device 102 is configured for cryotherapy, the console 104 may include a refrigerant reservoir (not shown) and may be configured to supply the refrigerant to the device 102. Similarly, when the device 102 is configured for chemical-based therapy (e.g., drug infusion), the console 104 may include a chemical reservoir (not shown) and may be configured to supply one or more chemicals to the device 102.

[0157] In some embodiments, the console 104 may include a controller 107 that is communicatively coupled to the neuromodulation device 102. However, in the embodiments described herein, the controller 107 may generally be carried by and disposed within the handle 118 of the neuromodulation device 102. The controller 107 is configured to initiate, terminate, and / or adjust the operation of one or more electrodes provided by the end effector 114 directly and / or through the console 104. For example, the controller 107 may be configured to execute an automatic control algorithm and / or receive control instructions from an operator (e.g., a surgeon or other medical professional or clinician). For example, the controller 107 and / or other components of the console 104 (e.g., a processor, memory, etc.) may include a computer-readable medium that carries instructions that, when executed by the controller 107, cause the device 102 to perform certain functions (e.g., apply energy in a particular manner, detect impedance, detect temperature, detect nerve location or anatomical structure, perform neural mapping, etc.). The memory includes one or more of a variety of hardware devices for volatile and non-volatile storage, and may include read-only and writable memory. For example, memory may include random access memory (RAM), CPU registers, read-only memory (ROM), and writable non-volatile memory such as flash memory, hard drives, floppy disks, CDs, DVDs, magnetic storage devices, tape drives, device buffers, etc. Memory is not a propagating signal separate from the underlying hardware; therefore, memory is non-transitory.

[0158] The console 104 can be further configured to provide feedback to the operator before, during, and / or after the treatment procedure via the mapping / assessment / feedback algorithm 110. For example, the mapping / assessment / feedback algorithm 110 can be configured to provide information associated with the location of nerves at the treatment site, the location of other anatomical structures (e.g., blood vessels) at the treatment site, the temperature at the treatment site during monitoring and regulation, and / or the effect of therapeutic neuromodulation on the nerves at the treatment site. In certain embodiments, the mapping / assessment / feedback algorithm 110 can include features for confirming the efficacy of the treatment and / or enhancing the desired performance of the system 100. For example, the mapping / assessment / feedback algorithm 110 in conjunction with the controller 107 and the end effector 114 can be configured to monitor nerve activity and / or temperature at the treatment site during treatment and automatically shut off energy delivery when the nerve activity and / or temperature reaches a predetermined threshold (e.g., a threshold decrease in nerve activity, a threshold maximum temperature when applying RF energy, or a threshold minimum temperature when applying cryotherapy). In other embodiments, the mapping / assessment / feedback algorithm 110 in conjunction with the controller 107 can be configured to automatically terminate therapy after reaching a predetermined maximum time, a predetermined maximum impedance or resistance rise of the target tissue (i.e., a predetermined maximum impedance of the target tissue compared to a baseline impedance measurement), and / or other thresholds of biomarkers associated with autonomic function. This and other information associated with the operation of the system 100 can be communicated to the operator via a display 112 (e.g., a monitor, touch screen, user interface, etc.) on the console 104 and / or a separate display (not shown) communicatively coupled to the console 104.

[0159] In various embodiments, the end effector 114 and / or other portions of the system 100 can be configured to detect various bioelectric parameters of tissue at the target site, and this information can be used by the mapping / evaluation / feedback algorithm 110 to determine the anatomical structure (e.g., tissue type, tissue location, vasculature, bone structure, foramen, sinuses, etc.) at the target site, locate neural structures, distinguish different types of neural structures, map the anatomical structure and / or neural structure of the target site, and / or identify a neuromodulation pattern of the end effector 114 with respect to the patient's anatomy. For example, the end effector 114 can be used to detect resistance, complex electrical impedance, dielectric properties, temperature, and / or other properties that indicate the presence of nerve fibers and / or other anatomical structures in the target area. In some embodiments, the end effector 114, together with the mapping / evaluation / feedback algorithm 110, can be used to determine the resistance (rather than impedance) of the tissue (i.e., the load) in order to more accurately identify the characteristics of the tissue. The mapping / evaluation / feedback algorithm 110 can determine the resistance of the tissue by detecting the actual power and current of the load (e.g., through the electrodes 136).

[0160] In some embodiments, the system 100 provides highly accurate and very highly precise resistance measurements, such as accurate measurements to one hundredth of an ohm (e.g., 0.01 Ω) for a 1-50 Ω range. The high resistance detection accuracy provided by the system 100 allows for detection of sub-microscale structures, including firing of neural structures, differences between neural structures and other anatomical structures (e.g., blood vessels), and events of different types of neural structures. This information can be analyzed by the mapping / evaluation / feedback algorithm and / or controller 107 and communicated to an operator via a high-resolution spatial grid (e.g., on display 112) and / or other type of display to identify neural structures and other anatomical structures at the treatment site and / or indicate predicted neuromodulation areas based on ablation graphics with respect to the mapped anatomical structures.

[0161] As previously described, in some embodiments, each electrode 136 can be operated independently of the other electrodes 136. For example, each electrode can be activated individually and the polarity and amplitude of each electrode can be selected by an operator or a control algorithm executed by the controller 107. Selective independent control of the electrodes 136 allows the end effector 114 to detect information and deliver RF energy to a highly customized area. For example, a selected portion of the electrodes 136 can be activated to target specific nerve fibers in a specific area, while other electrodes 136 remain inactive. In some embodiments, for example, the electrodes 136 can be activated on a portion of the second segment 124 adjacent to the tissue at the target site, and the electrodes 136 that are not close to the target tissue can remain inactive to avoid applying energy to non-target tissue. In addition, the electrodes 136 can be individually activated to stimulate or therapeutically modulate certain areas in a specific pattern (e.g., by multiplexing) at different times, which facilitates the detection of anatomical parameters on the area of ​​interest and / or therapeutic neuromodulation after adjustment.

[0162] The electrodes 136 may be electrically coupled to the energy generator 106 via a wire (not shown) extending from the electrodes 136 through the shaft 116 and to the energy generator 106. When each electrode 136 is independently controlled, each electrode 136 is coupled to a corresponding wire extending through the shaft 116. This allows each electrode 136 to be independently activated for stimulation or neuromodulation to provide precise ablation patterns, and / or individually detected by the console 104 to provide information specific to each electrode 136 for neural or anatomical detection and mapping. In other embodiments, multiple electrodes 136 may be controlled together, so that multiple electrodes 136 may be electrically coupled to the same wire extending through the shaft 116. The energy generator 16 and / or a component operably coupled thereto (e.g., a control module) may include a custom algorithm to control the activation of the electrodes 136. For example, the RF generator may deliver approximately 200-100 W of RF power to the electrodes 136, and while doing so, activate the electrodes 136 in a predetermined pattern selected based on the position of the end effector 114 relative to the treatment site and / or the identified location of the target nerve. In other embodiments, the energy generator 106 delivers lower levels of power (e.g., less than 1 W, 1-5 W, 5-15 W, 15-50 W, 50-150 W, etc.) for stimulation and / or higher levels of power. For example, the energy generator 106 can be configured to deliver 1-3 W stimulation energy pulses through the electrodes 136 to stimulate a specific target in the tissue.

[0163] As previously described, the end effector 114 may further include one or more temperature sensors disposed on the flexible first and second segments 122, 124 and / or other portions of the end effector 114 and electrically coupled to the console 104 via a wire (not shown) extending through the shaft 116. In various embodiments, the temperature sensor may be positioned proximate to the electrode 136 to detect the temperature at the interface between the tissue at the target site and the electrode 136. In other embodiments, the temperature sensor may penetrate the tissue at the target site (e.g., a penetrating thermocouple) to detect the temperature at a depth within the tissue. The temperature measurement may provide feedback to the operator or system regarding the effect of therapeutic neuromodulation on the tissue. For example, in some embodiments, the operator may want to prevent or reduce damage to the tissue at the treatment site (e.g., nasal mucosa), so the temperature sensor may be used to determine whether the tissue temperature reaches a predetermined threshold of irreversible tissue damage. Once the threshold is reached, the application of therapeutic neuromodulation energy may be terminated to allow the tissue to remain intact and avoid significant tissue shedding during wound healing. In certain embodiments, energy delivery may be automatically terminated based on a mapping / evaluation / feedback algorithm 110 stored on a console 104 operably coupled to the temperature sensor.

[0164] In some embodiments, the system 100 can determine the location and / or morphology of neural structures and / or other anatomical structures before treatment, so that therapeutic neuromodulation can be applied to a precise area including the target neural structure while avoiding negative effects on non-target structures such as blood vessels. As described in further detail below, the system 100 can detect various bioelectric parameters in the area of ​​interest (e.g., in the nasal cavity) to determine the location and morphology of various neural structures (e.g., different types of neural structures, neuronal directionality, etc.) and / or other tissues (e.g., glandular structures, blood vessels, bone regions, etc.). In some embodiments, the system 100 is configured to measure biopotentials. To this end, one or more electrodes 136 are placed in contact with the epithelial surface at the area of ​​interest (e.g., the treatment site). Electrical stimulation (e.g., a constant or pulsed current of one or more frequencies) is applied to the tissue by one or more electrodes 136 at or near the treatment site, and the voltage and / or current differences of various different frequencies between different electrode pairs 136 of the end effector 114 can be measured to produce a spectral profile or map of the detected biopotential, which can be used to identify different types of tissues (e.g., blood vessels, neural structures, and / or other types of tissues) in the area of ​​interest. For example, a current (i.e., direct current or alternating current) can be applied to a pair of electrodes 136 adjacent to each other, and the resulting voltage and / or current between the other adjacent electrode pairs 136 is measured. It should be appreciated that the current injection electrodes 136 and the measuring electrodes 136 need not be adjacent, and that modifying the spacing between the two current injection electrodes 136 can affect the depth of the recorded signal. For example, closely spaced current injection electrodes 136 provide recorded signals associated with tissue deeper from the tissue surface, compared to current injection electrodes 136 spaced farther apart providing recorded signals associated with tissue at a shallower depth. Recordings from electrode pairs with different spacings can be merged to provide additional information on the depth and localization of anatomical structures.

[0165] Further, the complex impedance and / or resistance measurements of the tissue at the area of ​​interest can be directly detected from the current-voltage data provided by the biopotential measurements while applying different levels of frequency current to the tissue (e.g., through the end effector 114), and this information can be used to map the neural structure and anatomical structure using frequency differential reconstruction. Applying stimulation of different frequencies will target different stratified layers or cell bodies or cell clusters. For example, at high signal frequencies (e.g., electrical injection or stimulation), the cell membrane of the neural structure does not hinder the flow of current, and the current passes directly through the cell membrane. In this case, the measurements (e.g., impedance, resistance, capacitance and / or inductance) generated are functions of intracellular and extracellular tissue and fluid. At low signal frequencies, the membrane hinders the flow of current to provide different defining features of the tissue, such as the shape of the cell or the intercellular spacing. The stimulation frequency can be in the megahertz range, the kilohertz range (e.g., 400-500kHz, 450-480kHz, etc.) and / or other frequencies coordinated with the characteristics of the tissue being stimulated and the device being used. The detected complex impedance or resistance levels from the region of interest may be displayed to the user (eg, via display 112) to visualize certain structures based on the stimulation frequency.

[0166] Further, the inherent morphology and composition of the anatomical structures in the nasal region react differently to different frequencies, so a specific frequency can be selected to identify a very specific structure. For example, the morphology or composition of the targeted structure for anatomical mapping may depend on whether the cells or other structures of the tissue are membranous, layered and / or annular. In various embodiments, the applied stimulation signal can have a predetermined frequency coordinated with a specific neural structure, such as the level of myelination and / or the morphology of myelination. For example, the myelin sheath of the second axon parasympathetic nerve structure is poorer than that of the sympathetic nerve or other structure, so compared with the sympathetic nerve, there will be a distinguishable response (e.g., complex impedance, resistance, etc.) about the selected frequency. Therefore, applying signals of different frequencies to the target site can distinguish between targeted parasympathetic nerves and non-targeted sensory nerves, thus providing a highly specific target site for neural mapping before and after treatment and / or neural assessment after treatment. In some embodiments, neural and / or anatomical mapping includes measuring data at the relevant area at at least two different frequencies to identify certain anatomical structures, so that the measurement is first performed based on the response to the injection signal with a first frequency, and then the measurement is performed again based on the injection signal with a second frequency different from the first frequency. For example, a hypertrophic (i.e., characteristic of a disease state) submucosal target has a different conductivity or dielectric constant at two frequencies compared to "normal" (i.e., healthy) tissue. The complex conductivity can be determined based on one or more measured physiological parameters (e.g., complex impedance, resistance, dielectric measurements, dipole measurements, etc.) and / or observation of one or more attributes or signatures that are believed to be known. In addition, the system 100 can also apply neuromodulatory energy at one or more predetermined frequencies coordinated with the target neural structure through the electrode 136 to provide highly targeted ablation of the selected neural structure associated with the one or more frequencies. This highly targeted neuromodulation also reduces the collateral effects of the neuromodulatory treatment on non-target sites / structures (e.g., blood vessels) because the targeted signal (having a frequency coordinated with the target neural structure) will not have the same modulatory effect on the non-target structure.

[0167] Accordingly, the system 100 can use bioelectrical properties, such as complex impedance and resistance, before, during, and / or after neuromodulation therapy to guide one or more treatment parameters. For example, impedance or resistance measurements can be used to confirm and / or detect contact between one or more electrodes 136 and adjacent tissue before, during, and / or after treatment. Impedance or resistance measurements can also be used to detect whether the electrode 136 is properly placed with respect to the target tissue type by determining whether the recorded spectrum has a shape consistent with the expected tissue type and / or whether the continuously collected spectrum is reproducible. In some embodiments, impedance or resistance measurements can be used to identify boundaries of the treatment zone (e.g., specific neural structures to be destroyed), anatomical landmarks, anatomical structures to be avoided (e.g., vascular structures or neural structures that should not be destroyed), and other aspects of delivering energy to tissue.

[0168] Bioelectric information can be used to generate spectrum profiles or graphs of different anatomical features organized at the target site, and anatomical drawings can be visualized in 3D or 2D images through display 112 and / or other user interfaces to guide the selection of appropriate treatment sites. This neural and anatomical drawing allows system 100 to accurately detect and therapeutically regulate the postganglionic parasympathetic nerve fibers of the innervated mucosa at the numerous neural entry points of the nasal cavity. Further, because there are no clear anatomical markers to represent the position of SPF, accessory holes and small holes, neural mapping allows the operator to identify and therapeutically regulate nerves that cannot be identified without complex dissection of the mucosa. In addition, anatomical drawings also allow clinicians to identify certain structures (e.g., certain arteries) that clinicians may want to avoid during therapeutic neuromodulation. The neural and anatomical bioelectrical properties detected by system 100 can also be used to determine the real-time effects of therapeutic neuromodulation on the treatment site during and after treatment. For example, the mapping / evaluation / feedback algorithm 110 may also compare the location and / or activity of nerves detected before and after therapeutic neuromodulation and compare changes in nerve activity to predetermined thresholds to assess whether the application of therapeutic neuromodulation is effective at the treatment site.

[0169] In various embodiments, the system 100 may also be configured to map the expected therapeutic modulation pattern of the electrode 136 at a particular temperature, and in some embodiments, taking into account tissue characteristics based on an anatomical mapping of the target site. For example, depending on the target site and / or structure, the system 100 may be configured to map ablation patterns of a particular electrode ablation pattern at a 45° C. isotherm, a 55° C. isotherm, a 65° C. isotherm, and / or other temperatures / ranges (e.g., a temperature range from 45° C. to 70° C. or higher).

[0170] The system 100 can provide a three-dimensional view of such a projected ablation pattern of the electrodes 136 of the end effector 114 via the display 112. The ablation pattern drawing can define the area of ​​influence that each electrode 136 has on the surrounding tissue. The area of ​​influence can correspond to the tissue area that will be exposed to therapeutic modulation energy based on the defined electrode activation pattern (i.e., one, two, three, four or more electrodes on any given strut of the first and second segments 122, 124). In other words, the ablation pattern drawing can be used to display ablation patterns for any number of electrodes 136, any geometry of the electrode layout, and / or any ablation activation scheme (e.g., pulsed activation, multipolar / sequential activation, etc.).

[0171] In some embodiments, the ablation pattern can be configured such that each electrode 136 has an area of ​​influence that only surrounds the individual electrode 136 (i.e., a "dot" pattern). In other embodiments, the ablation pattern can be such that two or more electrodes 136 can be connected together to form a sub-grouped area of ​​influence that defines a peanut-shaped or linear shape between the two or more electrodes 136. In further embodiments, the ablation pattern can produce a broader or continuous pattern in which the area of ​​influence extends along multiple electrodes 136 (e.g., along each strut). In further embodiments, the ablation pattern can produce different areas of influence depending on the electrode activation mode, phase angle, target temperature, pulse duration, device structure, and / or other treatment parameters. A three-dimensional view of the ablation pattern can be output to a display 112 and / or other user interface to allow a clinician to visualize varying areas of influence based on different energy application durations, different electrode activation sequences (e.g., multiplexing), different pulse sequences, different temperature isotherms, and / or other treatment parameters. This information can be used to determine an appropriate ablation algorithm for a patient's specific anatomical structure. In other embodiments, a three-dimensional visualization of the region of influence can be used to show the area where the electrodes 136 detect data when measuring bioelectric properties for anatomical mapping. In this embodiment, the three-dimensional visualization can be used to determine which electrode activation pattern should be used to determine the desired property (e.g., impedance, resistance, etc.) in the desired area. In some embodiments, it may be better to use point evaluation, while in other embodiments, it may be more appropriate to detect information from a linear or larger continuous area.

[0172] In some embodiments, the mapped ablation graphics are superimposed on the anatomical drawing to identify which structures (e.g., neural structures, blood vessels, etc.) will be therapeutically regulated or otherwise affected by the treatment. An image can be provided to the surgeon that includes a digital illustration of a predicted or planned neuromodulation zone associated with previously identified anatomical structures in the relevant area. For example, the illustration can show a number of neural structures and determine which neural structures are expected to be therapeutically regulated based on the predicted neuromodulation zone. The expected therapeutically regulated neural structures can be shaded to distinguish them from unaffected neural structures. In other embodiments, different colors and / or other indicators can be used to distinguish the expected therapeutically regulated neural structures from the unaffected neural structures. In further embodiments, the predicted neuromodulation zone and surrounding anatomical structures (based on the anatomical drawing) can be shown in a three-dimensional view (and / or include different visualization features (e.g., color coding to identify certain anatomical structures, bioelectric properties of target tissues, etc.). The combined predicted ablation graphics and anatomical drawing can be output to a display 112 and / or other user interface to allow the clinician to select an appropriate ablation algorithm for the patient's specific anatomical structure.

[0173] The imaging provided by system 100 allows the clinician to visualize the ablation pattern prior to treatment and adjust the ablation pattern to target specific anatomical structures while avoiding other anatomical structures to prevent collateral effects. For example, the clinician can select a treatment pattern to avoid blood vessels, thereby reducing the exposure of the vessels to therapeutic neuromodulation energy. This reduces the risk of vessel damage or rupture, thereby preventing immediate or potential bleeding. Further, the selective energy application provided by nerve mapping reduces the collateral effects of therapeutic neuromodulation, such as tissue shedding during the wound healing period (e.g., 1-3 weeks after ablation), thereby reducing the risk of aspiration associated with neuromodulation procedures.

[0174] The system 100 can be further configured to apply (via the electrodes 136) neuromodulatory energy of a specific frequency that is coordinated with the target neural structure, and thereby specifically targets the desired neural structure over the non-target structure. For example, the specific neuromodulatory frequency can correspond to a frequency identified as corresponding to the target structure during neural mapping. As described above, the inherent morphology and composition of anatomical structures respond differently to different frequencies. Therefore, frequency-tuned neuromodulatory energy tailored to the target structure does not have the same modulatory effect on non-target structures. More specifically, the application of neuromodulatory energy of a target-specific frequency causes ion agitation in the target neural structure, thereby causing differences in osmotic potential of the targeted neural structure and dynamic changes in neuronal membrane potential (caused by differences in intracellular and extracellular fluid pressures). This results in degeneration, possibly vacuolar degeneration, and ultimately necrosis of the target neural structure, but is not expected to functionally affect at least some non-target structures (e.g., blood vessels). Thus, the system 100 can use neural structure specific frequencies to (1) identify the location of the target neural structure to plan an electrode ablation configuration (e.g., electrode geometry and / or activation pattern) that specifically focuses neuromodulation on the target neural structure; and (2) apply neuromodulation energy at a characteristic neural frequency to selectively ablate neural structures that are responsive to the characteristic neural frequency. For example, the end effector 114 of the system 100 can selectively stimulate and / or modulate parasympathetic nerve fibers, sympathetic nerve fibers, sensory fibers, α / β / δ fibers, C-fibers, anoxic ends of one or more of the foregoing fibers, insulated from non-insulated fibers (regions with fibers), and / or other neural structures. In some embodiments, the system 100 can also selectively target specific cells or cell regions during anatomical mapping and / or therapeutic modulation, such as smooth muscle cells, submucosal glands, goblet cells, and stratified cell regions within the nasal mucosa. Thus, the system 100 provides highly selective neuromodulation therapy specific to the targeted neural structure and reduces the collateral effects of the neuromodulation therapy on non-target structures (e.g., blood vessels).

[0175] The present disclosure provides a method for anatomical mapping and therapeutic neuromodulation. The method includes extending an end effector (i.e., end effector 114) in a region of interest ("region of interest"), such as in a portion of a nasal cavity. For example, end effector 114 can be extended so that at least some electrodes 136 are placed in contact with mucosal tissue at the region of interest. The extended device can then perform bioelectric measurements via electrodes 136 and / or other sensors to ensure that the desired electrodes are in proper contact with the tissue at the region of interest. In some embodiments, for example, system 100 detects impedance and / or resistance on electrode pairs 136 to confirm that the desired electrodes have appropriate surface contact with the tissue and that all electrodes 136 are operating correctly.

[0176] The method continues to optionally apply electrical stimulation to the tissue and detect the bioelectrical properties of the tissue to establish a baseline specification for the tissue. For example, the method may include measuring resistance, complex impedance, current, voltage, neural firing rate, neural magnetic field, muscle activation and / or other parameters indicating the location and / or function of neural structures and / or other anatomical structures (e.g., glandular structures, blood vessels, etc.). In some embodiments, the electrode 136 sends one or more stimulation signals (e.g., pulse signals or constant signals) to the area of ​​interest to stimulate neural activity and initiate action potentials. The stimulation signal may have a frequency coordinated with a specific target structure (e.g., a specific neural structure, glandular structure, blood vessel) that allows the location of the specific target structure to be identified. The specific frequency of the stimulation signal is a function of the host permeability, and therefore, applying a unique frequency will change the tissue attenuation and the depth of tissue that the RF energy will penetrate. For example, lower frequencies generally penetrate deeper into the tissue than higher frequencies.

[0177] The non-stimulating electrode pairs 136 of the end effector 114 can then detect one or more bioelectric properties of the tissue that appear in response to the stimulation, such as impedance or resistance. For example, an electrode array (e.g., electrodes 136) can be selectively paired together in a desired pattern (e.g., multiplexing electrodes 136) to detect bioelectric properties at a desired depth and / or over a desired area to provide a high level of spatial awareness at the area of ​​interest. In some embodiments, the electrodes 136 can be paired together in a time-sequential manner according to an algorithm (e.g., provided by the mapping / evaluation / feedback algorithm 110). In various embodiments, two or more different frequencies of stimulation can be injected into the tissue, and the resulting bioelectric response (e.g., action potential) in response to each injected frequency can be detected by different electrode pairs 136. For example, an anatomical or neural mapping algorithm can cause the end effector 114 to deliver pulsed RF energy of a specific frequency between different electrode pairs 136, and the resulting bioelectric responses can be recorded in turn in a time sequence until the desired area of ​​interest is fully mapped (i.e., "multiplexed"). For example, the end effector 114 can deliver stimulation energy of a first frequency through adjacent electrode pairs 136 over a predetermined time period (e.g., 1-50 milliseconds), and the resulting bioelectric activity (e.g., resistance) can be detected through one or more other electrode pairs 136 (e.g., spaced apart from each other to reach different depths within the tissue). The end effector 114 can then apply stimulation energy of a second frequency different from the first frequency, and the resulting bioelectric activity can be detected through the other electrodes. This can continue when the area of ​​interest has been adequately mapped at the desired frequency. As described in further detail below, in some embodiments, baseline tissue bioelectric properties (e.g., neural firing rate) are detected using a static detection method (without injection of a stimulation signal).

[0178] After detecting the baseline bioelectric properties, the information can be used to map the anatomical structure and / or function at the area of ​​interest. For example, the bioelectric properties detected by the electrode 136 can be mapped by the mapping / evaluation / feedback algorithm 110, and the anatomical map can be output to the user via the display 112. In some embodiments, the complex impedance, dielectric or resistance measurements can be used to map the parasympathetic nerves and optionally identify neural structures that are in an overactive state. The bioelectric properties can also be used to map other non-target structures and general anatomical structures such as blood vessels, bones and / or glandular structures. The anatomical location can be provided to the user (e.g., on the display 112) as a two-dimensional map (e.g., showing relative intensity, showing specific locations of potential target structures) and / or as a three-dimensional image. This information can be used to distinguish sub-micron, cellular-level structures and identify very specific target structures (e.g., overactive parasympathetic nerves). The method can also predict the ablation pattern of the end effector 114 based on different electrode neuromodulation schemes, and optionally superimpose the predicted neuromodulation pattern on the mapped anatomical structure to indicate to the user which anatomical structures will be affected by a specific neuromodulation scheme. For example, when the predicted neuromodulation pattern is displayed in relation to the mapped anatomical structure, the clinician can determine whether the target structure will be appropriately ablated and whether non-target structures (e.g., blood vessels) will be undesirably exposed to therapeutic neuromodulation energy. Thus, the method can be used to plan neuromodulation treatments to locate very specific target structures, avoid non-target structures, and select electrode neuromodulation protocols.

[0179] Once the target structure is located and the desired electrode neuromodulation scheme is selected, the method proceeds to apply therapeutic neuromodulation to the target structure. Neuromodulation energy can be applied to the tissue in a highly targeted manner that forms microlesions to selectively modulate the target structure while avoiding non-targeted blood vessels and allowing surrounding tissue structures to remain healthy for effective wound healing. In some embodiments, neuromodulation energy can be applied in a pulsed manner, allowing the tissue to cool down between modulation pulses to ensure proper modulation without undesirably affecting non-target tissue. In some embodiments, the neuromodulation algorithm can deliver pulsed RF energy in a time sequence in turn between different electrode pairs 136 until the predicted neuromodulation is completed (i.e., "multiplexing"). For example, the end effector 114 can deliver neuromodulatory energy (e.g., with a power of 5-10 W (e.g., 7 W, 8 W, 9 W) and a current of approximately 50-100 mA) through adjacent electrode pairs 136 until at least one of the following conditions is met: (a) the load resistance reaches a predefined maximum resistance (e.g., 350 Ω); (b) the thermocouple temperature associated with the electrode pair reaches a predefined maximum temperature (e.g., 80° C.); or (c) a predefined time period has elapsed (e.g., 10 seconds). After the predetermined conditions are met, the end effector 114 can move to the next electrode pair in the sequence, and the neuromodulatory algorithm can be terminated when all load resistances of the respective electrode pairs are at or above a predetermined threshold (e.g., 100 Ω). In various embodiments, RF energy of a predetermined frequency (e.g., 450-500 kHz) can be applied and is expected to initiate ion agitation of specific target structures while avoiding functional destruction of non-target structures.

[0180] During and / or after the neuromodulation treatment, the method continues to detect and optionally map post-treatment bioelectric properties of the target site. This can be performed in a manner similar to that described above. The post-treatment evaluation can indicate whether the target structure (e.g., an overactive parasympathetic nerve) is adequately modulated or ablated. If the target structure is not adequately modulated (i.e., if neural activity is still detected in the target structure and / or the neural activity has not decreased), the method can continue to apply therapeutic neuromodulation to the target again. If the target structure is adequately ablated, the neuromodulation procedure can be completed.

[0181] Examination of anatomical structure and function

[0182] Various embodiments of the present technology can include measuring bioelectrical properties, dielectric properties, and / or other properties of tissue at a target site to determine the presence, location, and / or activity of neural structures and other anatomical structures, and optionally mapping the locations of the detected neural structures and / or other anatomical structures. For example, the present technology can be used to detect glandular structures and optionally detect their mucosal function and / or other functions. The present technology can also be configured to detect vascular structures (e.g., arteries) and optionally detect their arterial function, volume pressure, and / or other functions. The mapping features discussed below can be incorporated into any system 100 and / or any other device disclosed herein to provide an accurate depiction of the nerves at the target site.

[0183] Neural and / or anatomical detection can be performed (a) prior to application of therapeutic neuromodulation energy to determine the presence or location of neural structures and / or other anatomical structures (e.g., blood vessels, glands, etc.) at the target site and / or to record a baseline level of neural activity; (b) during therapeutic neuromodulation, determine the real-time effects of energy application on neural fibers at the treatment site; and / or (c) after therapeutic neuromodulation to confirm the efficacy of treatment on the targeted structure (e.g., neural glands, etc.). This allows identification of very specific anatomical structures (even to the microscale or cellular level), thereby providing highly targeted neuromodulation. This enhances the efficacy and efficiency of neuromodulation treatment. In addition, anatomical mapping reduces the collateral effects of neuromodulation treatment on non-target sites. Thus, targeted neuromodulation prevents damage or rupture of blood vessels (i.e., prevents unwanted bleeding) and inhibits collateral damage to tissues that may be of concern during wound healing (e.g., when damaged tissue breaks off from the wall of the nasal wall).

[0184] In certain embodiments, the systems disclosed herein can use bioelectric measurements, such as impedance, resistance, voltage, current density, and / or other parameters (e.g., temperature) to determine anatomical structures at the target site, particularly neural, glandular, and vascular anatomical structures. Bioelectric properties can be detected after delivering stimulation (e.g., electrical stimulation, such as RF energy delivered through electrode 136; i.e., "dynamic" detection) and / or without delivering stimulation (i.e., "static" detection).

[0185] Dynamic measurements include various embodiments of stimulating and / or detecting primary and secondary effects of neural activation and / or propagation. Such dynamic embodiments involve elevated states of neural activation and propagation, and use such dynamic measurements to perform neural localization and functional identification with respect to adjacent tissue types. For example, a method of dynamic detection may include: (1) delivering stimulation energy to a treatment site via a treatment device (e.g., end effector 114) to stimulate parasympathetic nerves at the treatment site; (2) measuring one or more physiological parameters (e.g., resistance, impedance, etc.) at the treatment site via a measurement / sensing array of the treatment device (e.g., electrodes 136); (4) determining the relative presence and position of parasympathetic nerves at the treatment site based on the measurements; and (5) delivering ablation energy to the identified parasympathetic nerves to block the detected parasympathetic nerves.

[0186] Static measurements include various embodiments associated with specific native properties of the layered or cellular components at or near the treatment site. Static embodiments relate to the inherent biological and electrical properties of the tissue type at or near the treatment site, the layered or cellular components at or near the treatment site, and comparing the aforementioned two measurements to tissue types that are adjacent to the treatment site (and are not targeted by neuromodulation). This information can be used to localize specific targets (e.g., parasympathetic nerve fibers) and non-targets (e.g., blood vessels, sensory nerves, etc.). For example, a static detection method may include: (1) determining one or more baseline physiological parameters using a measurement / sensing array (e.g., electrode 136) of a treatment device prior to ablation; (2) geometrically identifying inherent tissue properties within a region of interest based on the measured physiological parameters (e.g., resistance, impedance, etc.); (3) delivering ablation energy to one or more nerves within the region of interest via the treatment device; (4) determining one or more intraoperative physiological parameters using a measurement / sensing array during the delivery of ablation energy; and (5) determining one or more postoperative physiological parameters using a measurement / sensing array after the delivery of ablation energy to determine the effectiveness of the delivered ablation energy in blocking the nerves that received the ablation energy.

[0187] After initial static and / or dynamic detection of the bioelectric properties, the location of the anatomical features can be used to determine the location of the treatment site relative to various anatomical structures in order to provide therapeutically effective neuromodulation of the targeted parasympathetic nasal nerve. The bioelectric properties and other physiological properties described herein can be detected by electrodes (e.g., electrodes 136 of the end effector 114), and electrode pairings on the device (e.g., the end effector 114) can be selected to obtain bioelectric data for a specific zone or region or a specific depth of the targeted area. Specific characteristics detected at or around the target neuromodulation site and associated methods for obtaining these characteristics are described below. These specific detection and mapping methods discussed below are described with reference to system 100, but these methods can be implemented on other suitable systems and devices that provide anatomical identification, anatomical mapping and / or neuromodulation treatment.

[0188] Neural recognition and mapping

[0189] In many neuromodulation procedures, it is beneficial to identify portions of nerves that fall within the zone of influence and / or area of ​​influence (referred to as a "zone of interest") of energy delivered by the neuromodulation device 102 and the relative three-dimensional location of the neural structures relative to the neuromodulation device 102. Characterizing portions of neural structures within the zone of interest and / or determining the relative location of neural structures within the zone of interest enables the clinician to (1) selectively activate target neural structures over non-target structures (e.g., blood vessels), and (2) sub-select specific targeted neural structures (e.g., parasympathetic nerves) over non-target neural structures (e.g., sensory nerves, subsets of neural structures, neural structures having certain compositions or morphologies). Target structures (e.g., parasympathetic nerves) and non-target structures (e.g., blood vessels, sensory nerves, etc.) can be identified based on intrinsic signatures of specific structures, which are defined by unique morphological components of the structures and bioelectric properties associated with these morphological components. For example, unique discrete frequencies can be associated with morphological components and can therefore be used to identify certain structures. Target structures and non-target structures can also be identified based on the relative bioelectric activation of the structures in order to sub-select specific neuronal structures. Further, target structures and non-target structures can be identified by the different detected responses of these structures to tailored injected stimuli. For example, the system described herein can detect the difference in the response size of the structure and the response of the anatomical structure to different stimuli (e.g., different frequencies of injected stimuli).

[0190] At least for the purposes of the present disclosure, a nerve can include the following portions defined based on their respective orientations relative to the region of interest: a terminating nerve structure (e.g., a terminating axon structure), a branching nerve structure (e.g., a branching axon structure), and a traveling nerve structure (e.g., a traveling axon structure). For example, a terminating nerve structure enters the region but does not exit. As such, the terminating nerve structure is the endpoint of neuronal signaling and activation. A branching nerve structure is a nerve that enters the region of interest and increases the number of nerves exiting the region of interest. A branching nerve structure is typically associated with a decrease in the relative geometry of the nerve bundle. A traveling nerve structure is a nerve that enters the region of interest and exits the region with substantially no change in geometry or value.

[0191] System 100 can be used to detect voltage, current, complex impedance, resistance, dielectric constant and / or conductivity associated with the compound action potential of a nerve to determine the relative position and proportion of the nerve within the area of ​​interest and / or draw a map thereof. Neuron cross-sectional area ("CSA") is expected to be due to the increase in axonal structure. Each axon is of standard size. Larger nerves (in cross-sectional dimensions) have more axons than nerves with smaller cross-sectional dimensions. In static and dynamic assessments, the compound action response from larger nerves is greater than that of smaller nerves. This is at least in part because the compound action potential is the cumulative action response of each axon. For example, when using static analysis, system 100 can directly measure the impedance or resistance of the nerve and draw a map thereof, and based on the determined impedance or resistance, determine the position of the nerve and / or the relative size of the nerve. In dynamic analysis, system 100 can be used to apply stimulation to the area of ​​interest and detect the dynamic response of the nerve structure to the stimulation. Using this information, system 100 can determine the impedance or resistance in the area of ​​interest and / or draw a map thereof to provide information related to the position of the nerve or the relative size of the nerve. The neural impedance map can be presented by showing different complex impedance levels at specific locations at different cross-sectional depths. In other embodiments, the neural impedance or resistance can be mapped into a three-dimensional display.

[0192] Identifying the portion and / or relative position of a nerve within a region of interest can inform and / or guide the selection of one or more treatment parameters (e.g., electrode ablation patterns, electrode activation plans, etc.) of the system 100 to improve treatment efficiency and efficacy. For example, during nerve monitoring and mapping, the system 100 can identify the directionality of the nerve based at least in part on the length of the nerve structure extending along the region of interest, the relative size of the nerve structure, and / or the direction of the action potential. The system 100 or the clinician can then use this information to automatically or manually adjust treatment parameters (e.g., selective electrode activation, bipolar and / or multipolar activation, and / or electrode positioning) to target specific nerves or nerve regions. For example, the system 100 can selectively activate specific electrodes 136, electrode combinations (e.g., asymmetric or symmetric), and / or adjust bipolar or multipolar electrode configurations. In some embodiments, the system 100 can adjust or select waveforms, phase angles, and / or other energy delivery parameters based on nerve portion / location mapping and / or nerve proportionality mapping. In some embodiments, the structure and / or properties of the electrode 136 itself (e.g., material, surface roughening, coating, cross-sectional area, perimeter, penetration, penetration depth, surface mount, etc.) can be selected based on the neural portion and proportional drawing.

[0193] In various embodiments, treatment parameters and / or energy delivery parameters can be adjusted to target on-axis or proximal traveling neural structures and / or avoid activation of traveling neural structures that are at least substantially perpendicular to the end effector 114. More portions of on-axis or proximal traveling neural structures are exposed to or subject to neuromodulation energy provided by the end effector 114 than perpendicular traveling neural structures where only discrete cross-sections are exposed to therapeutic energy. Thus, the end effector 114 is more likely to have a greater effect on on-axis or proximal traveling neural structures. Identification of neural structure locations (e.g., by complex impedance or resistance mapping) can also allow targeted energy delivery to traveling neural structures rather than branching neural structures (typically downstream of traveling neural structures) because traveling neural structures are closer to the origin of the nerve, and therefore, more nerves are affected by therapeutic neuromodulation, resulting in more efficient treatment and / or greater treatment efficacy. Similarly, identification of neural structure locations can be used to target traveling and branching neural structures relative to terminating neural structures. In some embodiments, treatment parameters can be adjusted based on detected neural locations to provide selective regional effects. For example, if the clinician only wants to affect a partial effect on a very specific anatomical structure or location, then a downstream portion of the neural structure can be targeted.

[0194] In various embodiments, the nerve position and / or the relative position of the nerve can be determined by detecting the nerve generation voltage and / or current over time. The array of electrodes 136 can be positioned to contact the tissue at the area of ​​interest, and the electrodes 136 can measure the voltage and / or current associated with the nerve generation. This information can be optionally plotted (e.g., on the display 112) to identify the position of the nerve in a hyperactive state (i.e., parasympathetic nerve tension is too large). Rhinitis is at least partially the result of excessive nerve discharge, because this hyperactive state can lead to hyperactive mucosal production and hyperactive mucosal secretion. Therefore, detecting the nerve discharge rate by voltage and current measurement can be used to locate the part of the area of ​​interest including hyperactive parasympathetic nerve function (i.e., nerves in a diseased state). This allows clinicians to locate specific nerves (i.e., nerves with excessive parasympathetic nerve tension) before neuromodulation treatment, rather than just targeting all parasympathetic nerves (including parasympathetic nerves in a non-diseased state) to ensure that the correct tissue is treated during neuromodulation treatment. Further, the firing rate of the nerve can be detected during or after the neuromodulation treatment so that the clinician can monitor changes in the firing rate of the nerve to confirm the efficacy of the treatment. For example, recording a decrease or elimination of the firing rate of the nerve after the neuromodulation treatment can indicate that the treatment is effective in therapeutically treating the hyperactive / diseased nerve.

[0195] In various embodiments, the system 100 can use dynamic activation to detect neural activity by injecting a stimulation signal (i.e., a signal that temporarily activates the nerve) via one or more electrodes 136 to cause an action potential, and other electrode pairs 136 can detect the bioelectric characteristics of the neural response. Using dynamic activation to detect neural structures involves detecting the location of the action potential within the region of interest by measuring the firing rate in the neuron and associated processes. The ability to digitally measure, outline, map, and / or image the rapid depolarization of neurons to generate an accurate activity index is a factor in measuring the firing rate in neurons and their processes. The action potential causes a rapid increase in voltage on the nerve fiber, and then the electrical pulse spreads along the fiber. When an action potential occurs, the conductivity of the nerve cell membrane changes to about 40 times the conductivity when the cell is at rest. During an action potential or neuronal depolarization, the membrane resistance decreases by about 80 times, allowing the applied current to also enter the intracellular space. On a group of neurons, this causes a net reduction in resistance during coherent neuronal activity (such as parasympathetic chronic response) because the intracellular space will provide additional conductive ions. The magnitude of this rapid change has been estimated as peripheral nerve bundles (eg, including nerves in the nasal cavity) have local resistivity changes with near DC values ​​of 2.8-3.7% being recorded.

[0196] Detection of neural structures using dynamic activation involves detecting the location of action potentials within a region of interest by measuring the firing rate in neurons and associated processes. The basis of each such discharge is an action potential, during which the neuronal membrane depolarizes by up to 110 mV or more, lasts for approximately 2 milliseconds, and is due to the transfer of micromolar amounts of ions (e.g., sodium and potassium) across the cell membrane. The complex impedance or resistance change due to the neuronal membrane drops from 1000 Ωcm to 25 Ωcm. The introduction of stimulation and subsequent measurement of the neural response can attenuate noise and improve the signal-to-noise ratio to accurately focus on the response area, thereby improving neural detection, measurement, and mapping.

[0197] In some embodiments, measured differences over time of physiological parameters (e.g., complex impedance, resistance, voltage) that can reduce errors can be used to create neural profiles, spectra, or maps. For example, the sensitivity of the system 100 can be improved because this process provides repeated averaging of the stimulation. Therefore, the mapping function output can be a unitless ratio between reference and test collated data at a single frequency and / or multiple frequencies and / or multiple amplitudes. Additional considerations may include multiple frequency evaluation methods that thus expand parameter assessments, such as resistivity, admittance, center frequency, or the ratio of extracellular resistivity to intracellular resistivity.

[0198] In some embodiments, the system 100 can also be configured to indirectly measure the electrical activity of neural structures to quantify the metabolic recovery processes that accompany action potential activity and to restore ion gradients to normal. These are related to the accumulation of ions in the extracellular space. Indirect measures of electrical activity can be about a thousand times larger (approximately millimolar) and are therefore easier to measure and can improve the accuracy of the measured electrical properties used to generate the neural map.

[0199] The system 100 can perform dynamic neural detection by detecting neural electrical voltage and / or current and, optionally, neural electrical rate over time in response to external stimulation of the nerve. For example, an array of electrodes 136 can be positioned in contact with tissue at an area of ​​interest, one or more electrodes 136 can be activated to inject a signal stimulating the nerve into the tissue, and other electrodes 136 of the electrode array can measure the neural voltage and / or current caused by the neural discharge in response to the stimulation. This information can optionally be plotted (e.g., on a display 112) to identify the location of the nerve, and in some embodiments, to identify parasympathetic nerves that are in a hyperactive state (e.g., indicating rhinitis or other diseased states). Dynamic detection of neural activity (voltage, current, discharge rate, etc.) can be performed before neuromodulation therapy to detect the target nerve location, thereby selecting the target site and treatment parameters to ensure that the correct tissue is treated during neuromodulation therapy. Further, dynamic detection of neural activity can be performed during or after neuromodulation therapy to allow clinicians to monitor changes in neural activity to confirm the efficacy of treatment. For example, documenting a reduction or elimination of neural activity following neuromodulation therapy may indicate that the therapy was effective in therapeutically treating a hyperactive / diseased nerve.

[0200] In some embodiments, the stimulation signal can be delivered to the vicinity of the target nerve by one or more penetrating electrodes (e.g., microneedles that penetrate tissue) associated with the end effector 114 and / or a separate device. The stimulation signal generates an action potential, causing smooth muscle cells or other cells to contract. The location and intensity of this contraction can be detected by the penetrating electrode, thereby indicating to the clinician the distance to the nerve and / or the location of the nerve relative to the stimulation needle electrode. In some embodiments, the stimulation electrical signal can have a voltage of typically 1-2 mA or greater and a pulse width of typically 100-200 microseconds or greater. Shorter stimulation pulses allow for better differentiation of detected contractions, but may require a larger current. The greater the distance between the electrode and the targeted nerve, the more energy required for stimulation. The stimulation and detection of contraction intensity and / or location make it possible to identify how close or far the electrode is from the nerve, and can therefore be used to spatially localize the nerve. In some embodiments, a varying pulse width can be used to measure the distance to the nerve. As the needle gets closer to the nerve, the pulse duration required to cause a response becomes shorter and shorter.

[0201] In order to locate the nerve through muscle contraction detection, the system 100 can change the pulse width or amplitude to change the energy of the stimulation delivered to the tissue through the penetrating electrode (energy = pulse-width * amplitude). By changing the stimulation energy and monitoring muscle contraction via the penetrating electrode and / or other types of sensors, the system 100 can estimate the distance to the nerve. If a large amount of energy is required to stimulate the nerve / contract the muscle, the stimulation / penetrating electrode is farther away from the nerve. As the stimulation / penetrating electrode moves closer to the nerve, the energy required to cause muscle contraction will decrease. For example, a penetrating electrode array can be positioned in the tissue of the area of ​​interest, and one or more electrodes can be activated to apply stimulation at different energy levels until they cause muscle contraction. Using an iterative process, the nerve is localized (e.g., by a mapping / evaluation / feedback algorithm 110).

[0202] In some embodiments, system 100 can measure muscle activation caused by nerve stimulation (e.g., via electrode 136) to determine nerve localization for nerve mapping without using penetrating electrodes. In this embodiment, the therapeutic device targets varicosities of smooth muscle cells around the submucosal glands and vascular distribution, followed by compound muscle action potentials. This can be used to sum the voltage responses from individual muscle fiber action potentials. The shortest latency is the time from the stimulation artifact to the start of the response. The corresponding amplitude is measured from the baseline to the negative peak, measured in millivolts (mV). The neural latency (mean ± SD) of adults is typically in the range of about 2-6 milliseconds, more typically in the range of 3.4 ± 0.8 milliseconds to about 4.0 ± 0.5 milliseconds. In addition to the group evaluation using the alternative nasal cavity, a comparative assessment can then be performed that compares the output at each time interval (especially before and after energy delivery). This is expected to provide an accurate assessment of the absolute value of neural function performance, as muscle action / activation can be used to infer neural action / activation, whereas muscle action / activation is a secondary effect or by-product, whereas neural function is an absolute performance measure.

[0203] In some embodiments, the system 100 can record the neural magnetic field outside the nerve to determine the internal current of the nerve without physically destroying the neural membrane. Without being bound by theory, the contribution of the current inside the membrane to the magnetic field is two orders of magnitude of the contribution of the external current to the magnetic field, and the contribution of the current inside the membrane is essentially negligible. Neural electrical stimulation in series with the measurement of the magnetic composite action field ("CAF") can produce the sequential position of the current dipoles, so that the location of the conductive change can be estimated (e.g., by the method of least squares). Using a visual representation of the magnetic contour map (e.g., by the display 112) can show normal or abnormal neural characteristics (e.g., normal can be equivalent to a characteristic quadrupole pattern propagating along the nerve), and therefore indicate which nerves are in a diseased, overactive state and suitable for neuromodulation targets.

[0204] During magnetic field detection, an array of electrodes 136 can be positioned in contact with tissue at the area of ​​interest, and optionally, one or more electrodes 136 can be activated to inject electrical stimulation into the tissue. When a nerve in the area of ​​interest discharges (in response to stimulation or in the absence of stimulation), the nerve generates a magnetic field (e.g., similar to a current-carrying wire), and thus the changing magnetic field indicates the neural firing rate of the nerve. The changing magnetic field caused by the neural discharge can cause a current detected by a nearby sensor wire (e.g., sensor 314) and / or a wire associated with the nearby electrode 136. By measuring this current, the magnetic field strength can be determined. The magnetic field can optionally be mapped (e.g., on a display 112) to identify the location of the nerve before neuromodulation treatment and select a target nerve (a nerve with excessive parasympathetic tone) to ensure that the desired nerve is treated during neuromodulation treatment. Further, magnetic field information can be detected during or after neuromodulation treatment, so that clinicians can monitor changes in neural firing rates to confirm the efficacy of treatment.

[0205] In other embodiments, the magnetic field of the nerve is measured with a Hall probe or other suitable device, which can be integrated into the end effector 114 and / or a part of a separate device delivered to the area of ​​interest. Alternatively, instead of measuring the voltage in the second wire, the Hall probe can be used to measure the changing magnetic field in the original wire (i.e., the nerve). The current passing through the Hall probe will be turned in the semiconductor. This will cause a voltage difference between the top portion and the bottom portion, which can be measured. In some aspects of this embodiment, three orthogonal planes are utilized.

[0206] In some embodiments, the system 100 can be used to induce an electromotive force (“EMF”) in a line (i.e., a frequency selective circuit, such as a tunable / LC circuit) that is tuned to the resonant frequency of a nerve. In this embodiment, the nerve can be considered a current carrying line, and the discharge action potential is a varying voltage. This induces a varying current, which in turn induces a varying magnetic flux (i.e., a magnetic field perpendicular to the line). According to Faraday's law of induction / Faraday's principle, the varying magnetic flux induces an EMF (including a varying voltage) in a nearby sensor line (e.g., integrated into the end effector 114, sensor 314, and / or other structure), and the varying voltage can be measured by the system 100.

[0207] In further embodiments, the sensor wire (e.g., sensor 314) is an inductor and thus provides an increase in magnetic connection between the nerve (i.e., the first wire) and the sensor wire (i.e., the second wire), with more turns for increasing effect (e.g., V2, rms = V1, rms (N2 / N1)). Due to the changing magnetic field, a voltage is induced in the sensor wire, and this voltage can be measured and used to estimate current changes in the nerve. Certain materials can be selected to increase the efficiency of EMF detection. For example, the sensor wire can include a soft iron core or other high magnetic permeability material for the inductor.

[0208] During detection of induced EMF, the end effector 114 and / or other devices including sensor wires are positioned in contact with tissue at the area of ​​interest, and optionally, one or more electrodes 136 can be activated to inject electrical stimulation into the tissue. When a nerve in the area of ​​interest discharges (in response to stimulation or in the absence of stimulation), the nerve generates a magnetic field (e.g., similar to a current carrying wire) that induces a current in the sensor wire (e.g., sensor 314). This information can be used to determine the location of the nerve and / or map the nerve (e.g., on the display 112) to identify the location of the nerve prior to neuromodulation treatment and select target nerves (nerves with excessive parasympathetic tone) to ensure that the desired nerves are treated during neuromodulation treatment. EMF information can also be used during or after neuromodulation treatment so that the clinician can monitor changes in nerve firing rate to confirm treatment efficacy.

[0209] In some embodiments, the system 100 can detect the magnetic field and / or EMF generated at a selected frequency corresponding to a specific type of nerve. The frequency of the detected signal, and by extension the associated nerve type, can be selected based on the external resonant circuit. When the external circuit matches the magnetic field frequency of a specific nerve type and the nerve is firing, resonance occurs on the external circuit. In some manner, the system 100 can be used to locate a specific subgroup / type of nerves.

[0210] In some embodiments, the system 100 may include a variable capacitor frequency selection circuit to identify the location and / or map a specific nerve (e.g., parasympathetic nerve, sensory nerve, nerve fiber type, nerve subgroup, etc.). The variable capacitor frequency selection circuit may be defined by other features of the sensor 314 and / or the end effector 114. Nerves have different resonant frequencies based on their function and structure. Therefore, the system 100 may include a tunable LC circuit having a variable capacitor (C) and / or a variable inductor (L) that can be selectively tuned to the resonant frequency of the desired nerve type. This allows detection of neural activity associated only with the selected nerve type and its associated resonant frequency. Tuning can be achieved by moving the core in and out of the inductor. For example, the tunable LC circuit can tune the inductor by: (i) changing the number of coils around the core; (ii) changing the cross-sectional area of ​​the coils around the core; (iii) changing the length of the coils; and / or (iv) changing the magnetic permeability of the core material (e.g., from air to core material). A system including such a tunable LC circuit provides a high degree of propagation and discrimination not only in the activation of neural signals but also in the type of neural activated and the frequency of neural firing.

[0211] Anatomy Drawing

[0212] In various embodiments, the system 100 is further configured to provide minimally invasive anatomical mapping, which uses focused energy current / voltage stimulation from a spatially localized source (e.g., electrode 136) to cause changes in the conductivity of tissue at the region of interest and detect the resulting biopotential and / or bioelectrical measurements (e.g., by electrode 136). The current density in the tissue changes in response to changes in the voltage applied by the electrode 136, which produces current changes that can be measured with the end effector 114 and / or other parts of the system 100. The results of the bioelectrical and / or biopotential measurements can be used to predict or estimate relative absorption profile determination to predict or estimate tissue structure in the region of interest. More specifically, each cell construct has a unique conductivity and absorption curve that can indicate the type of tissue or structure, such as bone, soft tissue, blood vessels, nerves, nerve types, and / or certain neural structures. For example, different frequencies are attenuated differently by different types of tissue. Accordingly, by detecting the absorbed current in the area, the system 100 can determine the underlying structure, and in some cases, determine the underlying structure at the submicroscale, cellular level that allows highly specialized target localization and mapping. This highly specific target identification and mapping improves the efficacy and efficiency of neuromodulation therapy while also enhancing the safety of the system 100 to reduce collateral effects on non-target structures.

[0213] To detect the electrical and dielectric properties of the tissue (e.g., resistance, complex impedance, conductivity, and / or dielectric constant as a function of frequency), the electrode 136 and / or another electrode array is placed on the tissue at the area of ​​interest, and an internal or external source (e.g., generator 106) applies stimulation (current / voltage) to the tissue. The electrical properties of the tissue between the source electrode and the receiving electrode 136 are measured, as well as the current and / or voltage at each receiving electrode 136. These individual measurements can then be converted into an electrical map / image / contour of the tissue and visualized for the user on the display 112 to identify relevant anatomical features and, in some embodiments, the location of the generating nerve. For example, the anatomical drawing can be set as a color-coded or grayscale three-dimensional or two-dimensional map showing different intensities of certain bioelectrical properties (e.g., resistance, impedance, etc.), or the information can be processed to draw a map of the actual anatomical structure for the clinician. This information can also be used to monitor the progress of the treatment with respect to the anatomical structure during the neuromodulation treatment, and to confirm the success of the treatment after the neuromodulation treatment. In addition, anatomical mapping provided by bioelectric and / or biopotential measurements can be used to track changes in non-target tissue (e.g., blood vessels) due to neuromodulation therapy to avoid negative side effects. For example, a clinician can identify when the treatment begins to ligate a vessel and / or damage tissue and modify the treatment to avoid bleeding, harmful tissue ablation, and / or other negative side effects.

[0214] In addition, the current threshold frequency used to identify a specific target can subsequently be used when applying therapeutic neuromodulatory energy. For example, neuromodulatory energy can be applied at specific current threshold frequencies that are specific to target neurons and are distinguishable from other non-targets (e.g., blood vessels, non-target nerves, etc.). Application of ablation energy at a target-specific frequency generates an electric field that creates ion agitation in the target neural structure, thereby causing differences in the osmotic potential of the targeted neural structure. These osmotic potential differences cause dynamic changes in neuronal membrane potential (caused by differences in intracellular and extracellular fluid pressures), leading to vacuolar degeneration of the targeted neural structure and ultimately necrosis. Using highly targeted threshold neuromodulatory energy to initiate degeneration allows the system 100 to deliver therapeutic neuromodulation to a specific target while maintaining the function of surrounding blood vessels and other non-target structures.

[0215] In some embodiments, the system 100 can be further configured to detect bioelectric properties of tissue by non-invasively recording changes in resistance during neuronal depolarization in order to map neural activity using electrical impedance, resistance, bioimpedance, conductivity, dielectric constant, and / or other bioelectrical measurements. Without being bound by theory, when a nerve depolarizes, the cell membrane resistance decreases (e.g., decreases by approximately 80×) so that current will pass through open ion channels and enter the intracellular space. Otherwise, the current will remain in the extracellular space. For non-invasive resistance measurements, the tissue can be stimulated by applying a current less than 100 Hz, such as applying a 1 Hz constant current square wave with an amplitude less than 25% (e.g., 10%) of the threshold for stimulating neuronal activity, thereby preventing or reducing the possibility that the current does not cross into the intracellular space or stimulating at 2 Hz. In either case, the resistance and / or complex impedance is recorded by recording voltage changes. A complex impedance or resistance map or contour of the area can then be generated.

[0216] For impedance / conductivity / dielectric constant detection, the electrode 136 and / or another electrode array can be placed on the tissue at the area of ​​interest, and an internal or external source (e.g., the generator 106) applies stimulation to the tissue, and the voltage and / or current at each receiving electrode 136 is measured. Different frequencies of stimulation can be applied to isolate different types of nerves. These various measurements can then be converted into an electrical map / image / contour of the tissue and visualized for the user on the display 112 to identify relevant anatomical features. Nerve mapping can also be used during neuromodulation therapy to select specific nerves for treatment, monitor the progress of treatment with respect to nerves and other anatomical structures, and confirm treatment success.

[0217] In some embodiments of the above-described neural and / or anatomical detection methods, the surgery may include comparing intraoperative physiological parameters with baseline physiological parameters and / or other previously acquired intraoperative physiological parameters (within the same energy delivery phase). This comparison can be used to analyze changes in the state of the treated tissue. The intraoperative physiological parameters may also be compared with one or more predetermined thresholds, for example, to indicate when to stop delivering therapeutic energy. In some embodiments of the present technology, the measured baseline, intraoperative parameters, and postoperative parameters include complex impedance. In some embodiments of the present technology, postoperative physiological parameters are measured after a predetermined time period to allow electric field effects (ion agitation and / or thermal thresholds) to dissipate, thereby facilitating accurate assessment of the treatment.

[0218] In some embodiments, the above-mentioned anatomical mapping method can be used to distinguish the depth of soft tissue in the nasal mucosa. The depth of the mucosa on the nasal concha is large and the depth outside the nasal concha is shallow, therefore, identifying the depth of the tissue in the present technology also identifies the position in the nasal mucosa and identifies the target when it is precise. Further, by providing a microscale spatial impedance mapping of epithelial tissue as described above, the inherent unique signatures of the stratified layers or cell bodies can be used when identifying the relevant areas. For example, different areas have larger or smaller specific structural groups, such as submucosal glands, so the target area can be identified by identifying these structures.

[0219] In some embodiments, system 100 includes additional features that can be used to detect anatomical structures and map anatomical features. For example, system 100 can include an ultrasound probe for identifying neural structures and / or other anatomical structures. Ultrasound with higher frequencies provides higher resolution, but with less penetration depth. Accordingly, the frequency can be varied to achieve the appropriate depth and resolution for neural / anatomical localization. Functional identification can rely on spatial pulse length ("SPL") (wavelength multiplied by the number of pulse cycles). Axial resolution (SPL / 2) can also be determined to locate nerves.

[0220] In some embodiments, the system 100 can be further configured to emit stimulation with selective parameters that inhibit rather than fully stimulate neural activity, for example, in embodiments where the intensity and duration of extracellular neural stimulation are selected and controlled, there is a state in which the extracellular current can hyperpolarize the cell, so that spiking behavior is inhibited rather than stimulated (i.e., a full action potential is not achieved). Both ion channel models HH and RGC show that cells can be hyperpolarized by appropriately designed extracellular burst stimulation rather than prolonged stimulation. In any embodiment of neural detection and / or modulation described herein, this phenomenon can be used to inhibit rather than stimulate neural activity.

[0221] In various embodiments, the system 100 may apply the anatomical mapping techniques disclosed herein to locate or detect targeted vasculature and surrounding anatomical structures before, during, and / or after treatment.

[0222] References throughout this specification to "one embodiment" or "an embodiment" are intended to include, in at least one embodiment, a particular feature, structure, or characteristic described in conjunction with that embodiment. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment. In addition, the various specific features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.

[0223] The terms and expressions which have been employed herein have been used as terms of description and not of limitation, and in the use of such terms and expressions, there is no intention to exclude any equivalents of the features described and illustrated (or portions thereof), and it is recognized that various modifications are possible within the scope of the claims. Accordingly, the claims are intended to cover all such equivalents.

[0224] Incorporation by reference

[0225] Other documents, such as patents, patent applications, patent publications, journals, books, papers, web page content, have been referenced and cited throughout this disclosure. All of these documents are hereby incorporated herein by reference in their entirety for all purposes.

[0226] Equivalent

[0227] Various modifications of the invention and many other embodiments thereof, in addition to those shown and described herein, will become apparent to those skilled in the art from the entire contents of this document, including references to scientific and patent documents cited herein. The subject matter herein contains important information, examples, and guidance that can be applicable to the practice of the invention in its various embodiments and their equivalents.

Claims

1. A device for treating a condition in a patient's nasal cavity, the device comprising: a multi-segment end effector operably associated with a shaft and configured to deliver energy to one or more target sites within a nasal cavity of the patient, the multi-segment end effector comprising a proximal segment spaced apart from a distal segment that is separate and distinct along a longitudinal axis on which a distal-most portion of the shaft is located, wherein each of the proximal segment and the distal segment is transformable between a retracted configuration and an extended, deployed configuration and includes an associated architecture in the extended, deployed configuration, Wherein, the proximal segment comprises: a plurality of first support structures extending in a first outward direction relative to the longitudinal axis of the shaft and cooperating to form an inwardly extending first concave shape when the proximal segment is in the expanded, deployed configuration; and A plurality of second support structures extend in a second outward direction relative to the longitudinal axis of the shaft and substantially opposite the first outward direction and cooperate to form a second inwardly extending concave shape when the proximal segment is in the expanded, deployed configuration.

2. The device of claim 1, wherein: the proximal segment comprising a plurality of electrodes provided by the plurality of first support structures and the plurality of second support structures and configured to deliver energy to tissue at a first target site; as well as The distal segment includes a third set of flexible support elements and a plurality of electrodes provided by the third set of flexible support elements and configured to deliver energy to tissue at a second target site.

3. The device as claimed in claim 2, wherein: The plurality of first support structures, the plurality of second support structures, and the third set of flexible support elements are configured to position one or more of the plurality of electrodes at the first and second target sites when the proximal segment and the distal segment are in the expanded deployed configuration.

4. The device as claimed in claim 3, wherein: When in the expanded deployed configuration, the plurality of first support structures comprises a first pair of struts, wherein each strut comprises an annular shape and extends upwardly; And the plurality of second support structures includes a second pair of struts, wherein each strut includes an annular shape and extends downwardly.

5. The device according to claim 3, wherein: When in the expanded deployed configuration, the third group of support elements includes a third group of struts, wherein each strut includes an annular shape extending outwardly to form an open-ended circumferential shape.

6. The device according to claim 3, wherein: The plurality of first support structures, the plurality of second support structures, and the third set of flexible support elements include deformable composite wires.

7. The device according to claim 6, wherein: The composite wire includes a shape memory material.

8. The device of claim 1, wherein: At least some of the plurality of electrodes are configured to deliver radio frequency (RF) energy to tissue at respective target sites within the nasal cavity, wherein the respective target sites are associated with parasympathetic innervation.

9. The device of claim 8, wherein: At least some of the plurality of electrodes are configured to deliver RF energy at levels sufficient to therapeutically modulate postganglionic parasympathetic nerves innervating nasal mucosa at innervated pathways within a nasal cavity of the patient.

10. The device of claim 9, wherein: The condition is selected from the group consisting of allergic rhinitis, non-allergic rhinitis, chronic rhinitis, acute rhinitis, chronic sinusitis, acute sinusitis, chronic rhinosinusitis, acute rhinosinusitis and drug-resistant rhinitis.

Images