Systems and methods for therapeutic nasal nerve modulation

Abstract

To provide systems and methods for suitable therapeutic nasal neuromodulation.SOLUTION: The invention generally relates to systems and methods for therapeutically modulating nerves within or associated with a nasal region of a patient for treatment of a rhinosinusitis condition. A device for treating a condition within a nasal cavity of a patient is provided, the device comprising a multi-segment end effector for delivering energy to one or more target sites within the nasal cavity of the patient. The multi-segment end effector includes a proximal segment that is separated from a distal segment.SELECTED DRAWING: Figure 2

Description

Technical Field

[0001] (Cross - Reference to Related Applications) This application claims the priority and 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; 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, each of which is incorporated herein by reference in its entirety for all purposes.

[0002] The present invention generally relates to systems and methods for treating medical conditions, and more particularly to therapeutically modulating nerves within a patient's nasal region for the treatment of rhinosinusitis conditions.

Background Art

[0003] Rhinitis is an inflammatory disease of the nose and is reported to affect up to 40% of the population. It is the fifth most common chronic disease in the United States. The most common and most impactful symptoms of rhinitis are nasal congestion and rhinorrhea. 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 pollen, pet dander, or dust. Non - allergic rhinitis is the occurrence of the common rhinitis symptoms of nasal congestion and rhinorrhea. Since non - allergic rhinitis is not an immune response, its symptoms are usually not seasonal and are often more persistent. The symptoms of rhinitis include nasal discharge, sneezing, and nasal itching, as well as nasal congestion.

[0004] While allergen avoidance and drug therapy are relatively effective in the majority of mild cases, these medications need to be taken long-term, incurring costs and side effects, and often have suboptimal effectiveness. For example, medications prescribed for rhinosinusitis have limited effectiveness and undesirable side effects such as sedation, irritation, taste disturbances, sore throat, nasal dryness, and other adverse effects.

[0005] Two modern surgical options exist: the delivery of thermal energy to the inflamed soft tissue, which results in tissue scarring and temporary volume reduction, improving nasal airflow; and microdebridement of the inflamed soft tissue, which results in tissue removal, also improving nasal airflow. Both options address nasal congestion as opposed to rhinorrhea and carry risks ranging from bleeding and scarring to the use of general anesthesia. [Overview of the Initiative] [Means for solving the problem]

[0006] The present invention recognizes that a problem with current surgical procedures is that such procedures are not precise in treating rhinitis and cause significant collateral damage. The present invention solves this problem by providing a device having a unique multi-stage end effector and a handle architecture that provides the operator with a high level of precise control and feedback during use of the device of the present invention. The multi-stage end effector is configured to complement biostructures at multiple different locations within the nasal cavity. The handle is configured with a shape associated with the architecture of the end effector when deployed, as well as with multiple ergonomic and functional features that improve device use and feedback, such as independent control of end effector deployment and energy delivery. The handle may also include one or more markings that provide the user with spatial orientation of the end effector while it is inside the nasal cavity. In this form, the present invention provides a device that can conform to anatomical variations within the nasal cavity while providing the operator with unprecedented control and guidance, enabling the operator to perform precise, minimally invasive, localized application of energy to one or more target sites within the nasal cavity, causing multi-point blockade of nerve signals without causing collateral damage or interference to other nerve structures.

[0007] Unlike other surgical treatments for rhinitis, the device of the present invention is minimally invasive. Therefore, the procedure can be performed in a laboratory setting under local anesthesia. The multi-stage endo-effector allows for targeting of autonomic nerve supply to the nasal turbinates, which will have a positive effect 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 instead of months). Because the treatment is precise with minimal collateral damage to surrounding tissues, patients will begin to feel symptom relief immediately following the treatment. It is fully expected that patients will be able to discontinue their drug therapy following this therapy.

[0008] The present invention includes a handheld device comprising a retractable and expandable multi-segment end-effector that, once delivered into one or more target sites within the nasal cavity, can expand to a specific shape and / or size corresponding to the nasal cavity and anatomical structures associated with the target sites. In particular, the end-effector includes at least a first flexible segment and a second flexible segment, each containing a specific geometric shape to complement the biostructure of a particular location within the nasal cavity when in its deployed configuration. Once deployed, the first and second segments include conforming to and complementing the shape of one or more anatomical structures at the particular locations, contacting and conforming to the shape of the particular locations. Thus, the first and second segments become precisely positioned within the nasal cavity, and subsequently, a precise focused application of RF thermal energy is delivered to one or more target sites via one or more electrodes, thereby therapeutically modulating associated neural structures. More specifically, the first and second segments, when in an extended configuration, have a shape and size specifically designed to place portions of the first and second segments, and therefore one or more electrodes associated therewith, in contact with a target site in the nasal cavity associated with postganglionic parasympathetic nerve fibers that distribute nerves to the nasal mucosa.

[0009] The handheld device further includes a shaft operably associated with an end effector and a handle operably associated with the shaft. The shaft may include a predetermined shape (i.e., bent or angled in a specific orientation) to assist the surgeon (or other medical professional) in placing the end effector at a target site. The handle includes an ergonomically designed grip portion that provides ambidextrous use for both left-handed and right-handed use, conforms to the anthropometric measurements of the hand, and allows at least one of an overhand grip style and an underhand grip style during use in a procedure. 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 deployment configuration and a second mechanism for controlling the energy output by the end effector. User inputs for the first and second mechanisms are positioned at a sufficient distance from each other during a procedure to allow simultaneous one-handed operation of both user inputs. Therefore, the handle adapts to various grip styles, providing a degree of comfort for the surgeon, thereby further improving the execution of the procedure and the overall outcome. Furthermore, the handle and / or shaft may include markings (e.g., text, symbols, color coding, etc.) that provide the surgeon with spatial orientation of the end effector while it is in the nasal cavity. In particular, multiple markings provided on the handle and / or shaft can provide visual indication of the spatial orientation of one or more portions of the first and second segments of the end effector when it is in a deployed configuration. Thus, during the initial placement of the end effector, when it is in a retracted configuration and enclosed within the shaft, the surgeon can rely on the markings on the handle and / or shaft as visual indication of the spatial orientation (e.g., linear, axial, and / or depth position) of the end effector prior to deployment, thereby ensuring that once deployed, the end effector, including both the first and second segments, is positioned in the intended location within the nasal cavity.

[0010] Therefore, the handheld device of the present invention provides a user-friendly, non-invasive means for treating rhinosinusitis conditions, including the precise focused application of RF thermal energy to a intended target site for therapeutic modulation of the intended nerve structure, without causing incidental, unintended damage or interference to other nerve structures. Thus, the effectiveness of the Vidian nerve sectioning procedure can be achieved using the system and method of the present invention without the drawbacks discussed above. Most notably, the handheld device provides surgeons with a user-friendly, non-invasive, and precise means for treating such conditions by targeting only those specific nerve structures associated with rhinorrhea and other symptoms of rhinosinusitis, namely the postganglionic parasympathetic nerves distributing nerves to the nasal mucosa, thereby disrupting the parasympathetic supply and blocking parasympathetic tension. Therefore, such treatment is effective in treating rhinosinusitis conditions while greatly reducing the risk of incidental damage or interference to other nerve fibers, thereby reducing the possibility of unintended complications and side effects.

[0011] One aspect of the present invention provides a device for treating a patient's nasal cavity condition. The device includes a multi-segment end-effector for delivering energy to one or more target sites within the patient's nasal cavity. The multi-segment end-effector includes a proximal segment separated from a distal segment.

[0012] In some embodiments, the proximal segment comprises 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 comprises 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. The proximal and distal segments are each convertible between a retracted configuration and an extended-deployed configuration such that, when the first and second sets of flexible support elements are in an unfolded configuration, one or more of the individual first and second sets of electrodes are configured to position at the first and second target sites. In the extended-deployed configuration, the first set of support elements each comprises a first pair of upwardly extending, loop-shaped supports and a second pair of downwardly extending, loop-shaped supports. The second set of support elements, when in an extended deployment configuration, comprises a second set of support columns, each having a loop shape that extends outward and forms an open-end circumferential shape. The first and second sets of support elements comprise a deformable composite wire. The composite wire may include a shape memory material such as nitinol.

[0013] In some embodiments, first and second sets of electrodes are configured to deliver radio frequency (RF) energy to tissue at specific target sites within the nasal cavity, where the specific target sites are associated with parasympathetic nerve supply. For example, the first and second sets of electrodes may be configured to deliver RF energy at a level sufficient to therapeutically modulate postganglionic parasympathetic nerves that distribute nerves to the nasal mucosa in nerve supply pathways within the patient's nasal cavity. Nerve supply pathways may include microforamina in the patient's palatine bone. Conditions to be treated by the device may 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.

[0014] In some embodiments, the first segment of the multi-segment end effector has a first geometric shape for complementing a biological structure at a first location within the nasal cavity, and the second segment of the multi-segment end effector has a second geometric shape for complementing a biological structure at a second location within the nasal cavity. The first and second segments are each convertible between a retracted configuration and an extended unfolded configuration, such that a first set of flexible support elements of the first segment conforms to and complements the shape of a first anatomical structure at the first location when the first segment is in an unfolded configuration, and a second set of flexible support elements of the second segment conforms to and complements the shape of a second anatomical structure at the second location when the second segment is in an unfolded configuration. The first and second anatomical structures may include, but are not limited to, the inferior nasal conchae, middle nasal conchae, superior nasal conchae, inferior nasal meatus, middle nasal meatus, superior nasal meatus, pterygopalatine region, pterygopalatine fossa, sphenopalatine foramen, accessory sphenopalatine foramen, and sphenopalatine microforamen.

[0015] In some embodiments, the first segment of the multi-segment end effector is configured in an unfolded configuration to fit around at least a portion of the middle concha at an anterior position relative to the middle concha, and the second segment of the multi-segment end effector is configured in an unfolded configuration to contact multiple tissue locations within the cavity at a posterior position relative to the middle concha. For example, the first set of flexible support elements of the first segment conforms to and complements the shape of the lateral attachment and posterior inferior edge of the middle concha when the first segment is in an unfolded configuration, and the second set of flexible support elements of the second segment contacts multiple tissue locations within the cavity at a posterior position relative to the lateral attachment and posterior inferior edge of the middle concha when the second segment is in an unfolded configuration. Thus, when in an unfolded configuration, the first and second segments are configured to position one or more of the individual first and second sets of electrodes at one or more target sites relative to the middle concha and multiple tissue locations within the cavity behind the middle concha. Consequently, the first and second sets of electrodes are configured to deliver RF energy at levels sufficient to therapeutically modulate the postganglionic parasympathetic nerves, which distribute nerves to the nasal mucosa in the nerve supply pathways within the patient's nasal cavity.

[0016] Another aspect of the present invention provides a device for treating a patient's nasal cavity condition. The device comprises an end effector convertible between a retracted configuration and an extended 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 configuration, and a second mechanism separate from the first mechanism for controlling the energy output by the end effector.

[0017] In some embodiments, the handle includes an ergonomically designed grip portion having a shape, size, and contour that provides ambidextrous use for both left-handed and right-handed use, conforms to the anthropometric measurements of the hand, and allows at least one of an overhand grip style and an underhand grip style during use in a procedure. User inputs for the first mechanism may be located on the upper portion of the handle adjacent to the grip portion, and user inputs for the second mechanism may be located on the lateral portion of the handle adjacent to the grip portion. User inputs for the first and second mechanisms may be located at a sufficient distance from each other to allow simultaneous one-handed operation of both user inputs during a procedure.

[0018] In some embodiments, the first mechanism comprises a rack and pinion assembly that provides movement of an end effector between a retracted configuration and an extended 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 gearing ratio sufficient to maintain balance between stroke length and retraction and extension forces, thereby improving control over the extension of the end effector.

[0019] In some embodiments, the user-operated controller includes a slider mechanism operably associated with a rack and pinion rail assembly, wherein movement of the slider mechanism backward toward the proximal end of the handle results in a transition of the end effector to an extended configuration, and movement of the slider mechanism forward toward the distal end of the handle results in a transition of the end effector to a retracted configuration.

[0020] In some embodiments, the user-operated controller includes a scroll wheel mechanism operably associated with a rack and pinion rail assembly, wherein rotation of the wheel backward toward the proximal end of the handle results in a transition of the end effector to an extended configuration, and rotation of the wheel forward toward the distal end of the handle results in a transition of the end effector to a retracted configuration.

[0021] In some embodiments, the second mechanism comprises a user-operated controller configured to operate between an active and inactive position, thereby controlling the delivery of energy from the end effector. The user-operated controller can be multimodal in that it can operate between multiple positions that provide different functions / modes. For example, in response to a single user input (i.e., a single press of a button associated within the controller), the second mechanism may provide a reference juxtaposition / sensing check function prior to modulation. In response to pressing and holding the controller button for a predetermined time period, the energy output from the end effector may be activated. Furthermore, in response to double-tapping the controller button, the energy output may be deactivated.

[0022] In some embodiments, the handle may include a shape associated with the architecture of the end effector when deployed. For example, the handle may include a grip portion having a shape that generally provides the user with physical confirmation of the orientation of the end effector portion when deployed. For example, the end effector may include a first segment spaced apart from a second segment, and the first and second segments are each convertible between a retracted configuration and an extended, deployed configuration. The handle includes a grip portion comprising a top, a bottom, a side, a proximal end, and a distal end, and at least one of the top, bottom, and side of the grip portion of the handle is associated with the architecture of at least one of the first and second segments of the end effector when deployed. 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. In the unfolded configuration, the first set of support elements may include a first pair of upright struts, each having a loop shape, and a second pair of downright struts, each having a loop shape. The upper part of the grip portion may be associated, for example, with the first pair of upright struts, and the bottom of the grip portion may be associated with the second pair of downright struts. In the unfolded configuration, the second set of support elements may include a second set of struts, each having a loop shape that extends outward and forms an open-end circumferential shape. The distal end of the grip portion may be associated with the second set of outwardly extending struts.

[0023] In some embodiments, the handle and / or shaft may include one or more markings that provide the user with spatial orientation of the end effector while the end effector is inside the nasal cavity. For example, one or more markings on the handle or shaft may provide visual indication of the orientation of one or more parts of the end effector, specifically, indication of the spatial orientation of one or both of the first and second segments when deployed. The markings may include any visual marks such as text, symbols, color coding marks, etc. In some embodiments, multiple markings may be provided to provide visual indication of one or more parts of the first and second segments when deployed. For example, a first marking on either one or both of the handle and / or shaft may be associated with a first pair of supports extending upward of the first segment of the end effector, and a second marking may be associated with a second pair of supports extending downward of the first segment of the end effector. Therefore, while the first segment is in the nasal cavity in its deployed configuration, the first marking provides the user with a visual indication of the spatial orientation of the first pair of support structures extending upward, and the second marking provides the user with a visual indication of the spatial orientation of the second pair of support structures extending downward.

[0024] Another aspect of the present invention provides a method for treating a patient's nasal cavity condition. The method includes advancing a device comprising a multi-segment end-effector for delivering energy to one or more target sites within the patient's nasal cavity. The multi-segment end-effector comprises a proximal segment separated from a distal segment. The method further includes delivering energy to tissue at one or more target sites via the proximal and distal segments.

[0025] In some embodiments, the proximal segment comprises 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 comprises 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. The proximal and distal segments are each convertible between a retracted configuration and an extended-deployed configuration such that, when the first and second sets of flexible support elements are in an unfolded configuration, one or more of the individual first and second sets of electrodes are configured to position at the first and second target sites. In the extended-deployed configuration, the first set of support elements each comprises a first pair of upwardly extending, loop-shaped supports and a second pair of downwardly extending, loop-shaped supports. The second set of support elements, when in an extended deployment configuration, comprises a second set of support columns, each having a loop shape that extends outward and forms an open-end circumferential shape. The first and second sets of support elements comprise deformable composite wires and may include a shape memory material such as nitinol.

[0026] In some embodiments, the method further includes deploying the proximal and distal segments of a multi-segment end-effector at separate first and second target sites, thereby positioning one or more of the separate first and second sets of electrodes at the first and second target sites. Energy delivery via the proximal and distal segments includes delivering radio frequency (RF) energy via one or more of the separate first and second sets of electrodes to a level sufficient to therapeutically modulate the postganglionic parasympathetic nerves that distribute nerves to the nasal mucosa in the nerve innervation pathways within the patient's nasal cavity.

[0027] In some embodiments, the first segment of the end effector has a first geometric shape for complementing a biological structure at a first location within the nasal cavity, and the second segment has a second geometric shape for complementing a biological structure at a second location within the nasal cavity. Thus, the method may include deploying the first and second segments at individual first and second locations within the nasal cavity, and delivering energy via the first and second segments to tissue at one or more target sites for the first and second locations.

[0028] In some embodiments, the 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 when the first segment is in the deployed configuration, and the 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 when the second segment is in the deployed configuration. The first and second anatomical structures may include, but are not limited to, the inferior turbinate, middle turbinate, superior turbinate, inferior meatus, middle meatus, superior meatus, and the sphenopalatine foramen.

[0029] In some embodiments, the first segment of the end effector is configured in a deployed configuration to fit around at least a portion of the middle turbinate at a forward position relative to the middle turbinate, and the second segment of the end effector is configured in a deployed configuration to contact a plurality of tissue sites within the cavity at a rearward position relative to the middle turbinate. For example, a first set of flexible support elements of the first segment conforms to and complements the shape of the outer attachment portion of the middle turbinate at the forward position when the first segment is in the deployed configuration, and a second set of flexible support elements of the second segment conforms to and complements the shape of at least a second anatomical structure within the cavity behind the outer attachment portion of the middle turbinate when the second segment is in the deployed configuration. Thus, when in the deployed configuration, the first and second segments are configured to position one or more of the respective first and second sets of electrodes at one or more target sites relative to the middle turbinate and a plurality of tissue sites within the cavity behind the middle turbinate. Consequently, 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 in the innervation pathway within the patient's nasal cavity.

[0030] Another aspect of the present invention provides a method for treating a patient's nasal cavity condition. The method includes providing a therapeutic device comprising an end effector convertible between a retracted configuration and an extended 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 configuration, and a second mechanism separate from the first mechanism for controlling the energy output by 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 one or more target sites in the nasal cavity. The method further includes deploying the end effector at one or more target sites via user input using the first mechanism on the handle, and delivering energy from the end effector to tissue at one or more target sites via user input using the second mechanism.

[0031] In some embodiments, the handle has a shape associated with the architecture of the end effector when deployed. For example, the handle may include a grip portion having a shape that generally provides the user with physical confirmation of the orientation of a portion of the end effector when deployed. Thus, during the advancement of the end effector to one or more target sites in the nasal cavity, the method further includes the step of positioning the end effector to the one or more target sites, at least partially based on the orientation of the handle.

[0032] In some embodiments, the handle and / or shaft may include one or more markings that provide the user with spatial orientation of the end effector while the end effector is in the nasal cavity. For example, one or more markings on the handle or shaft may provide visual indication of the orientation of one or more portions of the end effector, specifically, indication of the spatial orientation of one or both of the first and second segments of the end effector when deployed. The markings may include any visual marks such as text, symbols, color coding marks, etc. In some embodiments, multiple markings may be provided to provide visual indication of one or more portions of the first and second segments when deployed. Thus, during the advancement of the end effector to one or more target sites in the nasal cavity, the method further includes the step of positioning the end effector to one or more target sites based at least partially on the orientation of the handle or shaft and one or more markings arranged around the handle or shaft.

[0033] Another aspect of the present invention provides a device for treating a patient's nasal cavity condition. The device includes a multi-segment end effector comprising at least a first retractable and expandable segment, which comprises a microelectrode array arranged around a plurality of strata. The strata have a bilateral geometric shape that conforms to and adapts to the anatomical structure of the nasal cavity when the first segment is in an expanded state. In particular, when in an expanded state, the strata contact multiple locations along multiple parts of the anatomical structure, and the electrodes of the microelectrode array are configured to release energy at a level sufficient to generate multiple microlesions in the tissue of the anatomical structure, blocking nerve signals to mucus-producing and / or mucosal congestion elements.

[0034] In some embodiments, the bilateral geometric shape comprises at least a first strut conforming to and adapting to a first side of an anatomical structure when the first segment is in an expanded state, and at least a second strut conforming to and adapting to a second side of the anatomical structure. When the first segment is in an expanded state, the first strut contacts multiple 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 release energy to a level sufficient to generate multiple distinct microlesions in the tissue along the first side of the anatomical structure. Similarly, when the first segment is in an expanded state, the second strut contacts multiple 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 release energy to a level sufficient to generate multiple distinct microlesions in the tissue along the second side of the anatomical structure. The anatomical structures may include, but are not limited to, the inferior nasal conchae, middle nasal conchae, superior nasal conchae, inferior nasal meatus, middle nasal meatus, superior nasal meatus, pterygopalatine region, pterygopalatine fossa, sphenopalatine foramen, accessory sphenopalatine foramen, and sphenopalatine microforamen.

[0035] In some embodiments, the first and second struts each have a loop shape and extend outward so as to move away from each other. The first and second struts are provided with deformable composite wires, the composite wires being made of a shape memory material. Each strut may include multiple electrodes of an electrode array positioned in separate and discrete portions of the strut. Thus, when extended, each strut may position at least one associated electrode of a microelectrode array in contact with tissue at separate and distinct locations on separate sides of an anatomical structure for energy delivery thereto. The electrodes of the microelectrode array are independently activated and controlled and thereby configured to deliver energy independently of each other.

[0036] Another aspect of the present invention provides a system for treating conditions within a patient's nasal cavity. The system includes a device comprising a multi-segment end effector for delivering energy to one or more target sites within a patient's nasal cavity and for sensing one or more properties of the one or more target sites. The multi-segment end effector includes a proximal segment spaced apart from a distal segment, and the proximal and distal segments each have specific geometric shapes to complement biostructures in the nasal cavity and at separate locations associated with the one or more target sites. 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 properties of the one or more target sites, process the data, and provide the operator with information related to the one or more target sites.

[0037] The console unit is configured to provide information associated with at least one of the following: identification and location of target and non-target nerve structures at one or more target sites, provided by at least one of the proximal and distal segments of the end effector, prior to therapeutic modulation therapy; identification and location of target and non-target anatomical structures at one or more target sites, provided by at least one of the proximal and distal segments of the end effector, prior to therapeutic modulation therapy; real-time feedback associated with the effectiveness of therapeutic modulation therapy on one or more target nerves and / or anatomical structures during therapeutic modulation therapy; and refeedback associated with the effectiveness of therapeutic modulation therapy on one or more target nerves and / or anatomical structures after therapeutic modulation therapy.

[0038] In some embodiments, the proximal and distal segments of the end effector each comprise a flexible support and a plurality of elements provided by the support.

[0039] For example, a first subset of multiple elements may be configured to deliver non-therapeutic stimulation energy to tissue at one or more target sites at frequencies that identify at least one of target neural structures, non-target neural structures, target anatomical structures, and non-target anatomical structures. A second subset of multiple elements may be configured to sense, in response to the stimulation energy, properties of at least one of target neural structures, non-target neural structures, target anatomical structures, and non-target anatomical structures. Properties may include, but are not limited to, at least one of physiological properties, bioelectrical properties, and thermal properties. Bioelectrical properties may include, but are not limited to, at least one of complex impedance, resistance, reactance, capacitance, inductance, dielectric constant, conductivity, nerve firing voltage, nerve firing current, depolarization, hyperpolarization, magnetic field, and induced electromotive force.

[0040] In some embodiments, the proximal segment of the end effector comprises a first set of flexible supports arranged in a first configuration, and the distal segment of the end effector comprises a second set of flexible supports arranged in a second configuration. The proximal and distal segments may each be convertible between a reclined configuration and an extended unfolded configuration, such that the first set of flexible supports conforms to and complements the shape of a first anatomical structure at a first location when the proximal segment is in an unfolded configuration, and the second set of flexible supports conforms to and complements the shape of a second anatomical structure at a second location when the distal segment is in an unfolded configuration. The first and second anatomical structures may include, but are not limited to, the inferior nasal concha, the middle nasal concha, the superior nasal concha, the inferior nasal meatus, the middle nasal meatus, the superior nasal meatus, the pterygopalatine region, the pterygopalatine fossa, the sphenopalatine foramen, the accessory sphenopalatine foramen, and the sphenopalatine microforamen.

[0041] The first and second sets of flexible supports may, when in a deployed configuration, be configured to position one or more of the individual elements provided by each at one or more individual target sites. For example, in an extended deployed configuration, the first set of flexible supports may each include a first pair of supports having a loop shape and extending upward, and a second pair of supports having a loop shape and extending downward. In an extended deployed configuration, the second set of flexible supports may each include a second set of supports having a loop shape extending outward and forming an open-end circumferential shape. Thus, the first and second sets of flexible supports may generally include a deformable composite wire, the composite wire being made of a shape memory material.

[0042] In some embodiments, the console unit is configured to detect and / or map the location of at least one of target nerve structures, non-target nerve structures, target anatomical structures, and non-target anatomical structures, and to control the delivery of therapeutic energy from at least one of the proximal and distal segments of the end effector in a modulation pattern based on the location of at least one of the target nerve structures, non-target nerve structures, target anatomical structures, and non-target anatomical structures. At least some of the elements provided by at least one of the proximal and distal segments are configured to deliver energy based on the modulation pattern to a level sufficient to therapeutically modulate one or more nerves associated with the location of the target nerve and / or target anatomical structure, while avoiding the location of the non-target nerve and / or target anatomical structure. At least some of the elements are configured to deliver energy based on the modulation pattern to a level sufficient to therapeutically modulate the non-target nerve and / or non-target anatomical structure.

[0043] In some embodiments, the console unit includes a controller configured to selectively control the energy output from elements of the proximal and / or distal segments of the end effector, some of which are independently activated and controlled, thereby configured to deliver energy independently of each other. The controller may be configured to modulate the energy output from elements of the proximal and / or distal segments of the end effector during its therapeutic modulation, at least in part, based on real-time feedback associated with the effectiveness of therapeutic modulation therapy on one or more target anatomical and / or neurostructural structures.

[0044] Another aspect of the present invention provides a method for treating a patient's nasal cavity condition. The method includes providing a therapeutic device comprising a multi-segment end effector including a proximal segment spaced apart from a distal segment and a visual marker. The method further includes, under image guidance, advancing the proximal and distal segments beyond the middle turbinate through the patient's nasal cavity and deploying the distal segment from a retracted configuration to an extended configuration. The proximal segment is then aligned with the middle turbinate under image guidance, with reference to the visual marker. Depending on the alignment, the method includes deploying the proximal segment around the middle turbinate. The method further includes advancing the proximal segment deployed toward the middle turbinate to establish contact and fix the proximal segment to the middle turbinate.

[0045] The unfolded proximal segment has a geometric shape to complement the shape of the middle concha and / or its lateral attachment, thereby ensuring that the unfolded proximal segment is fixed to the middle concha and / or its lateral attachment. For example, in some embodiments, the proximal segment comprises a set of flexible support elements that conform to and complement the shape of the middle concha and / or its lateral attachment when the proximal segment is in an unfolded extended configuration.

[0046] The method may further include the step of delivering energy via the proximal segment to the middle turbinate and / or its lateral attachment and / or the lateral wall of the nasal cavity to treat a 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, as well as combinations thereof. In some embodiments, the step of delivering energy from the proximal segment includes delivering radio frequency (RF) energy via one or more electrodes provided by the proximal segment to the tissue of the lateral wall surrounding the middle turbinate at one or more target sites, where one or more target sites are associated with one or more neurogenic pathways. In some embodiments, the RF energy is delivered via one or more electrodes provided by the proximal segment at a level sufficient to disrupt one or more neurogenic pathways associated with a condition such as a neurogenic pathway causing rhinorrhea and / or nasal congestion. In other embodiments, RF energy is delivered via one or more electrodes provided by the proximal segment to a level sufficient to therapeutically modulate one or more postganglionic parasympathetic nerves that distribute nerves to the nasal mucosa in a neurogenic pathway.

[0047] In some embodiments, the visual marker is provided by a shaft operably associated with a multi-segment end effector. The visual marker provides 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 markings, or equivalents. In some embodiments, the step of aligning the proximal segment with the middle concha includes, under image guidance, positioning the shaft and associated visual marker with respect to the middle concha and / or the posterolateral attachment of the middle concha, and / or the lateral wall of the nose.

[0048] Another aspect of the present invention provides a system for treating a patient's nasal cavity condition. The system includes a treatment device and an image-guided assembly that provides a visual representation of one or more parts of the treatment device and assists the user (i.e., a surgeon or other medical professional) in performing a procedure to treat a patient's nasal cavity condition.

[0049] The therapeutic device includes a multi-segment end effector comprising a proximal segment separated 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 the user with visual indication of the spatial orientation of at least the proximal segment under image guidance while the multi-segment end effector is in the patient's nasal cavity. The handle includes a controller mechanism for providing independent and controlled deployment of the proximal and distal segments, respectively, from a retracted configuration to an expanded configuration within the nasal cavity. The image-guided assembly provides a visual representation of at least the shaft and visual markers relative to the surrounding biostructure of the nasal cavity, thereby assisting the user in the deployment and positioning of at least the proximal segment within the nasal cavity.

[0050] 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 an extended configuration. The visual marker may include, for example, text, symbols, color markings, or equivalents.

[0051] The proximal segment, when in an extended configuration, may include geometric shapes to complement the shape of the middle turbinate and / or its lateral attachment, thereby ensuring that the extended proximal segment can establish sufficient contact with and firmly engage with the middle turbinate and / or its lateral attachment. For example, the proximal segment may include a set of flexible support elements that conform to and complement the shape of the middle turbinate and / or its lateral attachment when the proximal segment is in an extended configuration. The distal segment, when in an extended configuration, may include geometric shapes to complement the shape of another anatomical structure within the nasal cavity.

[0052] In some embodiments, the controller mechanism includes a rack and pinion assembly that, in response to user input from an associated user-operated controller, provides movement of at least one of the proximal and distal segments between a retracted configuration and an extended configuration. The rack and pinion assembly may include, for example, a set of gears for receiving user input from a user-operated controller and converting the user input into linear motion of a rack member operably associated with a multi-segment end effector.

[0053] In some embodiments, the controller mechanism may further include a return feature positioned relative to the proximal and distal segments and configured to provide the user with active feedback indicating the deployment of at least one of the proximal and distal segments. The active feedback may take the form of haptic feedback provided by the controller mechanism. For example, the haptic feedback may include an increase or decrease in resistance associated with user input, using the controller mechanism for the corresponding movement of at least one of the proximal and distal segments between a retracted configuration and an extended configuration, and / or configurations in between (i.e., multiple configurations between a fully retracted configuration and a fully extended configuration).

[0054] 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 and distal segments between a retracted configuration and an extended configuration, and further to provide the user with active feedback indicating the deployment of at least one of the proximal and distal segments. The friction-based feature may include a locking 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 and distal segments during its deployment. For example, constant friction may be sufficient to hold either the proximal or distal segment in a certain position as the segment transitions between the retracted and extended configurations, regardless of whether the user maintains contact with the user-operated controller. In other words, the user does not need to maintain contact with the user-operated controller to ensure that the proximal or distal segment maintains its position during its deployment. Rather, the user can simply interact with the user-operated controller and transition one of the proximal and distal segments to a desired configuration, and the constant friction provided by the locking mechanism is sufficient to maintain the configuration of the proximal or distal segment when the user has both hands free (i.e., eliminates any contact with the user-operated controller). The constant friction is still at a level sufficient to prevent undesirable movement of the proximal or distal segment (i.e., unintended crushing or expansion) while allowing the user to overcome such friction and move the proximal or distal segment to a desired configuration in response to user input using the user-operated controller.

[0055] In some embodiments, the user-operated controller includes a slider mechanism operably associated with a rack and pinion rail assembly, wherein movement of the slider mechanism in a first direction results in a transition of at least one of the proximal and distal segments to an extended configuration, and movement of the slider mechanism in a second opposite direction results in a transition of at least one of the proximal and distal segments to a retracted configuration.

[0056] In other embodiments, the user-operated controller includes a scroll wheel mechanism operably associated with a rack and pinion rail assembly, wherein rotation of the wheel in a first direction results in a transition of at least one of the proximal and distal segments to an extended configuration, and rotation of the wheel in a second opposite direction results in a transition of at least one of the proximal and distal segments to a retracted configuration. The present invention provides, for example, the following: (Item 1) A device for treating the condition of a patient's nasal cavity, wherein the device is A multi-segment end effector for delivering energy to one or more target sites within the patient's nasal cavity. Equipped with, The multi-segment end effector is a device comprising a proximal segment separated from a distal segment. (Item 2) The proximal segment comprises 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 comprises 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. The device described in item 1. (Item 3) The device according to item 2, wherein the proximal and distal segments are each convertible between a retracted configuration and an extended deployed configuration, such that when the first and second sets of the flexible support elements are in a deployed configuration, one or more of the individual first and second sets of electrodes are positioned at the first and second target sites. (Item 4) In the aforementioned expanded deployment configuration, the first set of support elements is A first pair of supports, each having a loop shape and extending upward, A second pair of supports, each having a loop shape and extending downward, and A device as described in item 3, comprising the features described in item 3. (Item 5) The device according to item 3, wherein, in the extended deployment configuration, the second set of support elements comprises a second set of struts, each of which has a loop shape extending outward and forming an open-end circumferential shape. (Item 6) The device according to item 3, wherein the first and second sets of the support elements comprise a deformable composite wire. (Item 7) The composite wire comprises a shape memory material, as described in item 6. (Item 8) The device according to item 1, wherein the first and second sets of electrodes are configured to deliver radio frequency (RF) energy to tissue at individual target sites within the nasal cavity, the individual target sites being associated with parasympathetic nerve supply. (Item 9) The device according to item 8, wherein the first and second sets of electrodes are configured to deliver RF energy at a level sufficient to therapeutically modulate the postganglionic parasympathetic nerves that distribute nerves to the nasal mucosa in the nerve innervation pathway within the patient's nasal cavity. (Item 10) The device according to item 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. (Item 11) A method for treating the condition of a patient's nasal cavity, wherein the method is The invention involves advancing a device comprising a multi-segment end effector for delivering energy to one or more target sites within the nasal cavity of the patient, wherein the multi-segment end effector comprises a proximal segment spaced apart from a distal segment, To deliver energy to the tissue at one or more target sites via the proximal and distal segments. Methods that include... (Item 12) The proximal segment comprises 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 comprises 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. The method described in item 11. (Item 13) The method according to item 12, wherein the proximal and distal segments are each convertible between a retracted configuration and an extended deployed configuration, such that when the first and second sets of the flexible support elements are in a deployed configuration, one or more of the individual first and second sets of electrodes are positioned at the first and second target sites. (Item 14) In the aforementioned expanded deployment configuration, the first set of support elements is A first pair of supports, each having a loop shape and extending upward, A second pair of supports, each having a loop shape and extending downward, and The method described in item 13, comprising: (Item 15) The method according to item 13, wherein, in the extended deployment configuration, the second set of support elements comprises a second set of struts, each of which has a loop shape extending outward and forming an open-end circumferential shape. (Item 16) The method according to item 13, wherein the first and second sets of the support elements comprise a deformable composite wire. (Item 17) The composite wire is the method described in item 16, comprising a shape memory material. (Item 18) The method according to item 13, further comprising deploying the proximal and distal segments of the multi-segment end effector at separate first and second target sites, thereby positioning one or more of the separate first and second sets of electrodes at the first and second target sites. (Item 19) The method according to item 18, comprising delivering radio frequency (RF) energy via one or more of the individual first and second sets of electrodes to a level sufficient to therapeutically modulate the postganglionic parasympathetic nerves that distribute nerves to the nasal mucosa in the nerve innervation pathway within the patient's nasal cavity. (Item 20) The method according to item 19, 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. [Brief explanation of the drawing]

[0057] [Figure 1A] Figures 1A and 1B are schematic diagrams of therapeutic neuromodulation systems for treating intranasal conditions using a handheld device, according to several embodiments of the present disclosure. [Figure 1B]Figures 1A and 1B are schematic diagrams of therapeutic neuromodulation systems for treating intranasal conditions using a handheld device, according to several embodiments of the present disclosure.

[0058] [Figure 2] Figure 2 is a schematic diagram of a console coupled to a handheld neuromodulator consistent with this disclosure, further illustrating a multi-segment end effector of a handheld device for delivering energy to tissue at one or more target sites within the nasal cavity via proximal and distal segments.

[0059] [Figure 3A] Figure 3A is a cross-sectional lateral view illustrating the biological structure of the lateral wall of the nose.

[0060] [Figure 3B] Figure 3B is a magnified lateral view of the nerves in the lateral wall of the nose shown in Figure 1A.

[0061] [Figure 3C] Figure 3C is a frontal view of the left palatine bone, illustrating the geometric shape of the micropores within the left palatine bone.

[0062] [Figure 4] Figure 4 is a side view of one embodiment of a handheld device for providing therapeutic nasal nerve modulation consistent with the present disclosure.

[0063] [Figure 5A] Figure 5A is an enlarged perspective view of a multi-segment end effector illustrating the first (proximal) segment and the second (distal) segment.

[0064] [Figure 5B] Figure 5B is an exploded perspective view of a multi-segment end effector.

[0065] [Figure 5C] Figure 5C is an enlarged top view of a multi-segment end effector.

[0066] [Figure 5D] Figure 5D is an enlarged side view of a multi-segment end effector.

[0067] [Figure 5E] Figure 5E is an enlarged front view (facing the proximal side) of the first (proximal) segment of the multi-segment end effector.

[0068] [Figure 5F] Figure 5F is a magnified frontal (proximal) view of the second (distal) segment of the multi-segment end effector.

[0069] [Figure 6] Figure 6 is a partially cross-sectional perspective view of a portion of a support element, illustrating exposed conductive wires that serve as energy delivery or electrode elements.

[0070] [Figure 7] Figure 7 is a cross-sectional view of a portion of the shaft of a handheld device obtained along line 7-7 in Figure 4.

[0071] [Figure 8] Figure 8 is a side view of the handle of a handheld device.

[0072] [Figure 9] Figure 9 is a side view of the handle, illustrating the internal components enclosed within.

[0073] [Figure 10] Figure 10 is a side view of the handle illustrating multiple markings on a portion of the handle to provide the user with spatial orientation of the end effector while the end effector is in the nasal cavity.

[0074] [Figure 11]Figure 11 is a perspective view of the shaft illustrating multiple markings on its distal portion to provide the user with spatial orientation of the end effector while the end effector is in the nasal cavity.

[0075] [Figure 12] Figure 12 is a partial cross-sectional side view illustrating one approach for delivering an end effector to a target site in the nasal region according to an embodiment of the present disclosure.

[0076] [Figure 13] Figure 13 is a flowchart illustrating one embodiment of a method for treating the condition of a patient's nasal cavity.

[0077] [Figure 14] Figure 14 is a flowchart illustrating another embodiment of a method for treating a patient's nasal cavity condition.

[0078] [Figure 15] Figure 15 is a flowchart illustrating another embodiment of a method for treating a patient's nasal cavity condition. [Modes for carrying out the invention]

[0079] There are various conditions related to the nasal cavity that can affect respiration and other functions of the nose. One of the most common conditions is rhinitis, defined as inflammation of the membranes covering the nose. Symptoms of rhinitis include nasal blockage, obstruction, nasal congestion, runny nose (e.g., rhinorrhea and / or postnasal drip), facial pain, facial pressure, and / or a reduced or complete loss of smell and / or taste. Sinusitis is another common condition involving inflammation or swelling of the tissues lining the sinuses, which can lead to complications. Rhinitis and sinusitis are frequently associated with each other because sinusitis often precedes rhinitis. Therefore, the term "rhinosinusitis" is often used to describe both conditions.

[0080] Depending on the duration and type of the system, rhinosinusitis can fall into different subtypes, including allergic rhinitis, non-allergic rhinitis, chronic rhinitis, acute rhinitis, recurrent rhinitis, chronic sinusitis, acute sinusitis, recurrent sinusitis, and drug-resistant rhinitis and / or sinusitis, in addition to combinations of one or more of the aforementioned conditions. Note that an acute rhinosinusitis condition is one in which symptoms persist for less than 12 weeks, while a chronic rhinosinusitis condition refers to symptoms that persist for longer than 12 weeks.

[0081] A recurrent sinusitis state refers to four or more episodes of acute sinusitis within a 12-month cycle, with periods of symptom resolution between each episode. Numerous environmental and biological causes of sinusitis exist. Non-allergic sinusitis can be caused, for example, by environmental irritants, medications, foods, hormonal changes, and / or deviated nasal septum. Triggers for allergic rhinitis can include exposure to seasonal allergens, perennial allergens occurring throughout the year, and / or occupational allergens. Therefore, sinusitis affects millions of people and is a major reason why patients seek medical treatment.

[0082] The present invention provides a system and method for therapeutically modulating nerves within the nasal region of a patient for the effective treatment of a rhinosinusitis condition. In particular, aspects of the present invention include a system and method for performing precise, minimally invasive, localized application of energy to one or more target sites within the nasal cavity to disrupt parasympathetic sensorimotor functions associated with a rhinosinusitis condition without causing collateral damage or interference to other nerve structures.

[0083] While many embodiments describe devices, systems, and methods for therapeutically modulating nerves in the nasal region for the treatment of rhinitis, it should be noted that other uses and embodiments are also within the scope of this disclosure. For example, at least some embodiments of this disclosure may be useful for treating other indications, such as chronic sinusitis and epistaxis. In particular, embodiments described herein may 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.

[0084] Figures 1A and 1B are schematic diagrams of a therapeutic neuromodulation system 100 for treating intranasal conditions using a handheld device 102, according to several embodiments of the present disclosure. The system 100 generally includes the neuromodulation device 102 and a neuromodulation console 104 to which the device 102 will be connected. Figure 2 is a schematic diagram of the console 104 coupled to the handheld neuromodulation device 102. As illustrated, the neuromodulation device 102 is a handheld device including a retractable and expandable 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 a patient 12 and positioned at a location associated with one or more target sites to be treated with therapeutic neuromodulation therapy. Note that the terms “end effector” and “therapeutic assembly” may be used synonymously throughout the present disclosure.

[0085] For example, a surgeon or other medical professional performing the procedure may use the handle 118 to manipulate and advance the shaft 116 within the nasal cavity, and the shaft 116 is configured to position at least its distal portion within the lumen at a treatment or target site within the nasal region. One or more target sites may generally be associated with postganglionic parasympathetic nerve fibers that distribute nerves to the nasal mucosa. The target site may also be a region, volume, or area where the target nerve is located, and may vary in size and shape depending on the patient's physiology. Once positioned, the end-effector 114 may be deployed and subsequently deliver energy to one or more target sites, thereby therapeutically modulating the nerve of interest, in particular the nerve associated with such a condition, in order to treat the rhinosinusitis condition. For example, the end-effector 114 may include at least one energy delivery element, such as an electrode, configured to therapeutically modulate the postganglionic parasympathetic nerve. For example, one or more electrodes may be provided by one or more parts of the end effector 114, and the electrodes may be configured to apply electromagnetic neuromodulation energy (e.g., radio frequency (RF) energy) to a 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 cryotherapy cooling, ultrasonic 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 refractive force.

[0086] 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 from the sensors, and / or transfer energy to the electrodes.

[0087] As shown, device 102 is operably coupled to console 104 via a wired connection such as cable 120. However, it should be noted that device 102 and console 104 may be operably coupled to each other via a wireless connection. Console 104 is configured to provide a variety of functions for neuromodulation device 102, which may include, but are not limited to, control, monitoring, supply, and / or otherwise support operations for neuromodulation device 102. For example, when neuromodulation device 102 is configured for electrode-based, thermal element-based, and / or transducer-based therapy, console 104 may include an energy generator 106 configured to generate RF energy (e.g., unipolar, bipolar, or multipolar RF energy), pulsed electrical energy, microwave energy, optical energy, ultrasonic energy (e.g., intraluminal ultrasound and / or HIFU), direct thermal energy, radiation (e.g., infrared, visible, and / or gamma radiation), and / or another preferred type of energy.

[0088] In some embodiments, the console 104 may include a controller 107 that is communicatively coupled to the neuromodulatory device 102. However, in the embodiments described herein, the controller 107 may generally be carried by a handle 118 of the neuromodulatory device 102 and provided inside it. The controller 107 is configured to start, stop, and / or adjust the operation of one or more electrodes provided by the end effector 114, directly and / or via the console 104. For example, the controller 107 may be configured to execute an automatic control algorithm and / or to receive control commands 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, when executed by the controller 107, carries commands, causes the device 102 to perform functions (e.g., apply energy in a specific manner, detect impedance, detect temperature, detect nerve location or anatomical structure, etc.), and carries commands. Memory includes one or more hardware devices for volatile and non-volatile storage, and can include both read-only and writable memory. For example, memory can 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, and device buffers. Memory is not a propagating signal isolated from the underlying hardware, and therefore memory is non-transient.

[0089] Console 104 may also be configured to provide feedback to the operator before, during, and / or after a therapeutic procedure via an evaluation / feedback algorithm 110. For example, the evaluation / feedback algorithm 110 may be configured to provide information associated with the temperature of the tissue at the treatment site, the location of nerves at the treatment site, and / or the effect of therapeutic neuromodulation on nerves at the treatment site. In one embodiment, the evaluation / feedback algorithm 110 may include features to confirm the effectiveness of the therapy and / or improve the desired performance of the system 100. For example, the evaluation / feedback algorithm 110, in conjunction with the controller 107, may be configured to monitor the temperature at the treatment site during therapy and automatically stop energy delivery when the temperature reaches a predetermined maximum value (e.g., when RF energy is applied) or a predetermined minimum value (e.g., when cryotherapy is applied). In other embodiments, the evaluation / feedback algorithm 110, in conjunction with the controller 107, may be configured to automatically terminate the treatment after a predetermined maximum time, a predetermined maximum impedance rise of the target tissue (i.e., compared to a reference impedance measurement), a predetermined maximum impedance of the target tissue, and / or other thresholds relating to biomarkers associated with autonomous function. Book 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) communicably coupled to the console 104, such as a tablet or monitor. The GUI 112 may generally provide action commands for the procedure, including instructing the operator to select the nasal cavity to be treated, indicating when the device 102 is primed and ready to perform the treatment, and indicating when the treatment is complete, and further providing the status of the treatment during the procedure.

[0090] For example, in some embodiments, the end effector 114 and / or other parts of the system 100 may be configured to detect various parameters of heterogeneous tissue at a target site, determine biostructures at the target site (e.g., tissue type, tissue location, vascular system, bone structure, foramina, sinuses, etc.), identify nerves and / or other structures, and enable nerve mapping. For example, the end effector 114 may be configured to detect impedance, dielectric properties, temperature, and / or other properties indicating the presence of nerve fibers in the target region. As shown in Figure 1, the console 104 may further include a monitoring system 108 configured to receive, process, and identify the presence, location, and / or neural activity of nerves at the target site, obtained by the end effector 114 and specifically sensed by appropriate sensors (e.g., temperature sensors and / or impedance sensors). The nerve monitoring system 108 can be operably coupled to the electrodes and / or other features of the end effector 102 via signal wires (e.g., copper wires) that extend through the cable 120 and along the length of the shaft 116. In other embodiments, the end effector 114 can be communicatively coupled to the nerve monitoring system 108 using other suitable means of communication.

[0091] The neuronal monitoring system 108 can determine the location and activity of nerves before therapeutic neuromodulation, determine a precise treatment area corresponding to the desired nerve location, determine the effect of therapeutic neuromodulation during treatment, and / or evaluate after treatment whether therapeutic neuromodulation treated the target nerve to the desired extent. This information can be used to make various decisions related to nerves adjacent to the target site, such as whether the target site is suitable for neuromodulation. In addition, the neuronal monitoring system 108 can also compare the detected nerve locations and / or activity before and after therapeutic neuromodulation, compare changes in nerve activity to predetermined thresholds, and assess whether the application of therapeutic neuromodulation was effective across the treatment site. For example, the neuronal monitoring system 108 can further determine the electroneurographic (ENG) signal based on recordings of the neuronal electrical activity obtained by the end-effector 114 before and after therapeutic neuromodulation. A statistically significant (e.g., measurable or significant) decrease in the ENG signal obtained after neuromodulation can serve as an indicator that the nerve has been sufficiently ablated. Additional features and functions of the neurosurveillance system 108, as well as other functions of the various components of the console 104, including an evaluation / feedback algorithm 110 for providing real-time feedback capabilities to ensure that the optimal therapy for a given treatment is administered, are described in at least U.S. Publication No. 2016 / 0331459 and U.S. Publication No. 2018 / 0133460, which are incorporated herein by reference to their respective contents as a whole.

[0092] As will be described in more detail herein, the neuromodulator 102 provides access to deep target sites within the nasal region, such as the approaching entry points of parasympathetic nerve fibers into the nasal cavity, thereby therapeutically modulating autonomous activity within the nasal cavity. In one embodiment, for example, the neuromodulator 102 can position an end-effector 114 in contact with a target site within the nasal cavity associated with postganglionic parasympathetic nerve fibers distributing nerves to the nasal mucosa.

[0093] Figure 3A is a cross-sectional lateral view illustrating the biological structure of the lateral wall of the nose, and Figure 3B is an enlarged lateral view of the nerves in the lateral wall of the nose shown in Figure 1A. The sphenopalatine foramen (SPF) is an opening or conduit defined by the palatine and sphenoid bones through which the sphenopalatine vessels and the posterior superior nasal nerve advance into the nasal cavity. More specifically, the orbital and sphenoid processes of the vertical plate of the palatine bone define the sphenopalatine notch, which is converted into the SPF by articulation with the surface of the body of the sphenoid bone.

[0094] The location of the submucosal fold (SPF) is highly variable within the posterior region of the lateral nasal cavity, making it difficult to visually identify the SPF. Typically, the SPF is located within the middle meatus (MM). However, anatomical variations also cause the SPF to be located within the superior meatus (SM) or at the junction of the superior and middle meatuses. In some individuals, for example, the lower boundary of the SPF is measured approximately 13 mm above the horizontal plate of the inferior turbinate (IT) and approximately 19 mm above the horizontal plate of the palatine bone (i.e., the nasal base), resulting in an average distance of approximately 64.4 mm from the nasal base to the SPF, and an approach angle of approximately 11.4° from the nasal base to the SPF. However, studies for precisely measuring the location of the SPF are of limited practical use due to the wide variation in its location.

[0095] Anatomical variations in the SPF are expected to correspond to alterations in autonomic and vascular pathways that traverse the nasal cavity. Generally, the posterior nasal nerve (also called the lateral posterior superior nasal nerve) from the pterygopalatine ganglion (PPG), also known as the sphenopalatine ganglion, enters the lateral nasal wall of the nasal cavity through the SPF, and the sphenopalatine artery is thought to pass through the SPF on the lateral nasal wall from the pterygopalatine fossa. The sphenopalatine artery branches into two main parts: the posterolateral nasal branch and the posterior nasal septal branch. The main branch of the posterolateral nasal artery proceeds inferiorly into the inferior turbinate GG (e.g., about 1.0 mm to 1.5 mm from the posterior tip of the inferior turbinate IT), while the other branch enters the middle turbinate MT and branches anteriorly and posteriorly.

[0096] Beyond the SPF, studies have shown that over 30% of human patients have one or more accessory foramina that also carry arteries and nerves into the nasal cavity. Accessory foramina are typically smaller than the SPF and located below it. For example, there may be one, two, three, or more branches of the posterior nasal artery and posterior nasal nerve extending through the corresponding accessory foramina. The variability in location, size, and number associated with accessory foramina, and the associated branching arteries and nerves that proceed through them, creates considerable uncertainty regarding the location of the vascular and nerve systems in the sphenopalatine region. Furthermore, native biostructures extending from the SPF often include deep inferior and / or superior grooves that carry nerve and arterial pathways, making it difficult to identify arterial and nerve branches. For example, grooves may extend beyond 5 mm in length, beyond 2 mm in width, and beyond 1 mm in depth, thereby generating sufficiently significant pathways to carry both arteries and nerves. Variations caused by grooves and accessory foramina within the sphenopalatine region make it extremely difficult for surgeons to identify and access arteries and nerves (located posterior to the arteries).

[0097] Recent microanatomical dissections of the pterygopalatine fossa (PPF) further demonstrate the highly variable biostructure of the region surrounding the SPF, exhibiting multiple efferent branches that project from the pterygopalatine ganglion (PPG), rather than individual postganglionic autonomic nerves (e.g., the posterior nasal nerve), distributing nerves to the orbital and nasal mucosa via numerous clusters of small nerve fiber bundles. Studies have shown that at least 87% of humans have microforamina and microbranchings in the palatine bone.

[0098] Figure 3C is a frontal view of the left palatine bone, illustrating, for example, the geometric shape of the microforamina and microbranchs within the left palatine bone. In Figure 3C, the filled areas represent nerves that proceed directly through the palatine bone, and the white circles represent nerves associated with distinctly different microforamina. Thus, Figure 3C illustrates that the medial portion of the palatine bone may contain at least 25 accessory posterolateral nerves.

[0099] The respiratory portion of the nasal mucosa consists of a certain type of ciliated columnar epithelium, accompanied by a basement membrane. Nasal secretions (e.g., mucus) are produced by goblet cells, submucosal glands, and exudates from plasma. Nasal mixed glands and blood vessels are highly regulated by parasympathetic innervation derived from Vidian and other nerves. Parasympathetic (cholinergic) stimulation via acetylcholine and vasoactive intestinal peptides generally results in mucus production. Therefore, parasympathetic innervation of the mucosa is primarily involved in submucosal gland activation / hyperactivation, venous congestion (e.g., stagnation), and increased blood flow to the blood vessels covering the nose. Thus, severing or modulating the parasympathetic pathways that distribute nerves to the mucosa is expected to reduce or eliminate submucosal gland hyperactivation and vascular congestion, which cause symptoms associated with rhinosinusitis and other indications.

[0100] As previously described herein, the postganglionic parasympathetic nerve fibers (i.e., the posterior superior nasal nerve) that supply nerves to the nasal mucosa were thought to proceed locally through the SPF as the sphenopalatine nerve-vascular bundle. The posterior nasal nerve is a branch of the maxillary nerve that supplies nerves to the nasal cavity via several smaller medial and lateral branches that extend through the mucosa of the superior and middle turbinates (ST, MT) to the nasal septum. The nasopalatine nerve is generally the largest of the medial posterior superior nasal nerves and passes anteroinferiorly in the vomeroid groove to the floor of the nasal cavity. From here, the nasopalatine nerve passes through the incisive fossa of the hard palate and communicates with the greater palatine nerve, which supplies nerves to the mucosa of the hard palate. The posterior superior nasal nerve passes over the maxillary nerve via its ganglion branches through the pterygopalatine ganglion (PPG) without synapsing.

[0101] Based on the understanding that the posterior nasal nerve locally traverses the SPF and distributes nerve to the nasal mucosa, surgical procedures are performed to selectively sever the posterior nasal nerve as it exits the SPF. However, as discussed above, the parasympathetic sinus pathway actually comprises individual branches distributing nerve to the nasal mucosa via multiple small nerve fiber bundles (i.e., accessory posterolateral nerves), rather than a single branch projecting from the pterygopalatine ganglion (PPG) and extending through the SPF. These branches are transmitted throughout the palatine bone through multiple fissures, accessory foramina, and microforamina, demonstrating anastomotic loops with both the SPF and other accessory nerves.

[0102] Therefore, only when the parasympathetic nerves traversing the SPF are severed will almost all patients (e.g., over 90% of patients) retain intact pro-paracrine fibers in the posterolateral mucosa, which would result in the persistence of symptoms that the nerve transection was intended to achieve.

[0103] Therefore, embodiments of the present disclosure are configured to therapeutically modulate nerves in precise focused treatment sites corresponding to the locations of branches extending through fissures, accessory foramina, and microforamina throughout the palatine bone (e.g., target region T shown in Figure 3B). In some 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 postoperative nasal crusting or dryness, as it allows clinicians to gradually increase the degree of anterior denervation through the wise preservation of orbitonasal cavity branches. Furthermore, embodiments of the present disclosure are also expected to maintain at least some degree of sympathetic tone by reserving some sympathetic contributions from the deep petrosal nerve and the internal perimacular artery plexus, leading to improved outcomes with respect to nasal obstruction. In addition, embodiments of the present disclosure are configured to target numerous parasympathetic entry points into the nasal region (e.g., accessory foramina, fissures, and microforamina) and provide complete resection of all anastomotic loops, thereby reducing long-term renervation rates.

[0104] Figure 4 is 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 convertible between a retracted configuration and an extended configuration, 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 114 includes at least a first segment 122 and a second segment 124 spaced apart from each other. The first segment 122 is generally located 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 located further from the distal end of the shaft 116 and is therefore sometimes referred to herein as the distal segment 124. The first and second segments 122 and 124 are each convertible between a retracted configuration, which includes a thin delivery state to facilitate intraluminal delivery of the end effector 114 to the treatment site in the nasal region, and an extended configuration, which includes an extended state as shown in Figure 4 and further illustrated in Figures 5A-5F. The handle 118 includes, at least, a first mechanism 126 for the deployment of the first and second segments 122 and 124 of the multi-segment end effector 114 from the retracted configuration to the extended configuration, and a second mechanism 128 separate from the first mechanism 124 for controlling the energy output by electrodes or other energy elements provided by either the first or second segments 122 and 124 of the end effector 114, specifically the first and / or second segments 122 and 124. The handheld device 102 may further include an auxiliary line 121 that can provide a fluid connection between a fluid source and the shaft 116, for example, so that fluid can be supplied to a target site via 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 so that the device 102 may have suction capabilities (via the distal end of the shaft 116).

[0105] Figures 5A, 5B, 5C, 5D, 5E, and 5F are enlarged views of the multi-segment end effector 114, illustrating various views of the first and second segments 122 and 124 in more detail. Figure 5A is an enlarged perspective view of the multi-segment end effector 114. Figure 5B is an exploded perspective view of the multi-segment end effector 114. Figures 5C and 5D are enlarged top and side views of the multi-segment end effector 114, respectively. Figure 5E is an enlarged front (proximal) view of the first segment 122 of the multi-segment end effector 114. Figure 5F is an enlarged front (proximal) view of the second segment 124 of the multi-segment end effector 114.

[0106] As shown in the figures, the first segment 122 includes at least a first set of flexible support elements, generally in the form of wires, arranged in the first configuration, and the second segment 124 includes a second set of flexible support elements, similarly in the form of wires, arranged in the second configuration. The first and second sets of flexible support elements include composite wires having conductive and elastic properties. For example, in some embodiments, the composite wires include shape memory materials such as nitinol. The flexible support elements may further include a highly lubricating coating that can enable desirable electrical insulation properties and a desirable low-friction surface finish. The first and second segments 122, 124 are each convertible between a retracted configuration and an extended, deployed configuration, so as to position one or more electrodes (see electrode 136 in Figures 5E and 5F) provided on the individual segments in contact with one or more target sites when the first and second sets of flexible support elements are in a deployed configuration.

[0107] As shown, in the extended deployment configuration, the first set of support elements for the first segment 122 includes at least a first pair of struts 130a, 130b, each having a loop (or lobe) shape and extending upward, and a second pair of struts 132a, 132b, each having a loop (or lobe) shape and generally extending downward in the opposite direction to at least the first pair of struts 130a, 130b. Note that the terms “upward” and “downward” are used to describe the orientation of the first and second segments 122, 124 relative to each other. More specifically, the first pair of struts 130a, 130b generally extend outward inclined in a first direction with respect to the longitudinal axis of the multi-segment end effector 114 and are spaced apart from each other. Similarly, the second pair of support columns 132a, 132b extend outward inclined directions in a second direction substantially opposite to the first direction with respect to the longitudinal axis of the multi-segment end effector, and are spaced apart from each other.

[0108] The second set of support elements for the second segment 124 includes a second set of struts 134(1), 134(2), 134(n) (about six struts), each having a loop shape that extends outward and forms an open-end circumferential shape when the configuration is extended. As shown, the open-end circumferential shape generally resembles a blooming flower, and each loop-shaped strut 134 may generally resemble a petal. Note that the second set of struts 134 may include any number of individual struts and is not limited to six as shown. For example, in some embodiments, the second segment 124 may include two, three, four, five, six, seven, eight, nine, ten, or more struts 134.

[0109] The first and second segments 122, 124, specifically struts 130, 132, and 134, include one or more energy delivery elements, such as multiple electrodes 136. It should be noted that any individual strut may include any number of electrodes 136 and is not limited to one electrode as shown. In the extended state, struts 130, 132, and 134 can position any number of electrodes 136 relative to tissue at a target site within the nasal region (e.g., adjacent to the palatine bone below the SPF). The electrodes 136 can apply bipolar or multipolar radio frequency (RF) energy to the target site to therapeutically modulate postganglionic parasympathetic nerves that distribute nerves to the nasal mucosa adjacent to the target site. In various embodiments, the electrodes 136 may be configured to apply pulsed RF energy using a desired duty cycle (e.g., 1 second on / 0.5 seconds off) to regulate the temperature rise within the target tissue.

[0110] The first and second segments 122, 124, and their associated struts 130, 132, and 134 can support the electrode 136 and have sufficient rigidity to position or press the electrode 136 against the tissue at the target site. In addition, the extended first and second segments 122, 124 can each press against surrounding anatomical structures adjacent to the target site (e.g., nasal conchae, palatine bone, etc.), and the individual struts 130, 132, and 134 can at least partially conform to the shape of adjacent anatomical structures to anchor the end effector 114. Furthermore, the expandability and conformability of the struts 130, 132, and 134 can facilitate the placement of the electrode 136 in contact with the surrounding tissue at the target site. The electrode 136 can be fabricated from platinum, iridium, gold, silver, stainless steel, platinum-iridium, cobalt-chromium, iridium oxide, polyethylenedioxythiophene (PEDOT), titanium, titanium nitride, carbon, carbon nanotubes, platinum gray, drawn-filled tubes (DFTs) with silver cores, and / or other suitable materials for delivering RF energy to the target tissue. In some embodiments, as illustrated in Figure 6, the strut may include an outer jacket surrounding a conductive wire, the outer jacket being selectively absent along the length of the strut, thereby exposing the underlying conductive wire to act as an energy-delivering element (i.e., electrode) and / or sensing element, as will be 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 control algorithm (e.g., performed by a controller 107 as described above herein). Selective independent control of electrodes 136 allows the end effector 114 to deliver RF energy to highly customized regions. For example, a selected portion of electrode 136 can be activated to target nerve fibers within a specific region, while other electrodes 136 remain inactive. In some embodiments, for example, electrode 136 may be activated across a portion of a second segment 124 adjacent to tissue at the target site, while electrodes 136 not adjacent to the target tissue remain inactive, thus avoiding the application of energy to non-target tissue. Such a configuration facilitates selective therapeutic modulation of nerves on the lateral wall of the nose within one nostril without applying energy to structures in other parts of the nasal cavity.

[0112] Electrode 136 is electrically coupled to the RF generator (e.g., generator 106 in Figure 1) via a wire (not shown) extending from electrode 136 through shaft 116 to the RF generator. When each electrode 136 is controlled independently, each electrode 136 is coupled to the corresponding wire extending through shaft 116. In other embodiments, multiple electrodes 116 can be controlled together, and thus multiple electrodes 116 can be electrically coupled to the same wire extending through shaft 116. As described above, the RF generator and / or components operably coupled thereto (e.g., a control module) may include custom algorithms for controlling the activation of electrode 136. For example, the RF generator may deliver RF power to electrode 136 at approximately 460–480 kHz (+ or -5 kHz), activating electrode 136 in a predetermined pattern selected based on the position of the end effector 114 relative to the treatment site and / or identified location of the target nerve. The RF generator provides bipolar low-power (10 watts with a maximum setting of 50 watts) RF energy delivery and can also provide multiplexing capability (across up to 30 channels).

[0113] Once deployed, the first and second segments 122, 124 conform to and complement the shape of one or more anatomical structures at specific locations, including contacting and conforming to the shape of those specific locations. Thus, the first and second segments 122, 124 are precisely positioned within the nasal cavity and subsequently deliver a precise focused application of RF thermal energy to one or more target sites via one or more electrodes 136, thereby therapeutically modulating the associated nerve structures. More specifically, when in an extended configuration, the first and second segments 122, 124 have shapes and sizes specifically designed to position portions of the first and second segments 122, 124, and therefore one or more electrodes 136 associated with them, in contact with target sites within the nasal cavity associated with postganglionic parasympathetic nerve fibers distributing nerves to the nasal mucosa.

[0114] For example, 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 when the first segment 122 is in an unfolded configuration, and 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 when the second segment is in an unfolded configuration. The first and second anatomical structures may include, but are not limited to, the inferior nasal concha, middle nasal concha, superior nasal concha, inferior nasal meatus, middle nasal meatus, superior nasal meatus, pterygopalatine region, pterygopalatine fossa, sphenopalatine foramen, accessory sphenopalatine foramen, and sphenopalatine microforamen.

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

[0116] For example, the first set of flexible support elements (i.e., struts 130 and 132) of the first segment conforms to and complements the shape of the lateral attachment and posterior inferior edge of the middle turbinate when the first segment 122 is in an unfolded configuration, and the second set of flexible support elements (i.e., struts 134) of the second segment 124 contacts multiple tissue locations within the cavity at a position posterior to the lateral attachment and posterior inferior edge of the middle turbinate when the second segment 124 is in an unfolded configuration. Thus, when in an unfolded configuration, the first and second segments 122 and 124 are configured to position one or more associated electrodes 136 at one or more target sites relative to the middle turbinate and multiple tissue locations within the cavity behind the middle turbinate. The electrodes 136 are configured to deliver RF energy at a level sufficient to therapeutically modulate the postganglionic parasympathetic nerves, which distribute nerves to the nasal mucosa in the nerve supply pathways within the patient's nasal cavity.

[0117] As illustrated in Figure 5E, the first segment 122 has a bilateral geometric shape. In particular, the first segment 122 includes two identical sides, a first side formed from struts 130a, 132a and a second side formed from struts 130b, 132b. This bilateral geometric shape allows at least one of the two sides to conform to and adapt to the anatomical structure within the nasal cavity when the first segment 122 is in an expanded state. For example, when expanded, the multiple struts 130a, 132a contact multiple locations along multiple parts of the anatomical structure, and the electrodes provided by the struts are configured to release energy to a level sufficient to generate multiple microlesions in the tissue of the anatomical structure, blocking nerve signals to mucus-producing and / or mucosally congestive elements. In particular, the struts 130a and 132a conform to and complement the shape of the lateral attachment and posterior inferior margin of the middle turbinate when the first segment 122 is in an unfolded configuration, thereby allowing both sides of the anatomical structure to receive energy from the electrodes. By having this independence between the first lateral configuration and the second lateral configuration (i.e., right and left), the first segment 122 is a true bilateral device. By providing a bilateral geometric shape, the multi-segment end effector 114 does not require a repeat-use configuration to treat the other side of the anatomical structure, as both sides of the structure are occupied simultaneously due to the bilateral geometric shape. The resulting micro-lesion patterns may be repeatable and predictable in both macro-elements (depth, volume, shape parameters, surface area), and can be controlled to establish low / high effects, as well as micro-elements, as will be described in further detail herein (thresholding of effects within the macro-envelope range can be controlled). The system of the present invention can further establish an internal gradient, which allows control over neural effects without affecting other cell bodies extensively, as will be described in more detail herein.

[0118] Figure 7 is a cross-sectional view of a portion of the shaft 116 of a handheld device obtained along line 7-7 in Figure 4. As shown, the shaft 116 may be constructed from multiple components to have the ability to restrain the end effector 114 in a retracted configuration (i.e., a low-profile delivery state) when the end effector 114 is retracted into the shaft 116, and further to provide a non-traumatic, low-profile, and durable means for delivering the end effector 114 to a target site. The shaft 116 includes a coaxial tube that extends from the handle 118 to the distal end of the shaft 116. The shaft 116 assembly is low-profile to ensure transnasal delivery of the therapy. The shaft 116 includes an outer sheath 138 surrounding a hypotube 140, which is further assembled over an electrode wire 129 surrounding an inner lumen 142. The outer sheath 138 serves as an interface between the biostructure and the device 102. The outer sheath 138 may generally include a low-friction PTFE liner to minimize 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 blaze along the length of the shaft 116 to provide flexibility while reserving kink resistance and further retaining column and / or tensile strength. For example, the outer sheath 138 may include a soft Pebax material that is non-traumatic and allows for smooth delivery through the nasal passage. The outer sheath 138 may further generally include orientation / marker markings on its outer surface at the distal end, the markings providing the 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, which can assist in positioning and deployment of the end effector 114.

[0119] The hypotube 140 is assembled along the electrode wire, starting within the handle 118 and extending to the proximal end of the end effector 114. The hypotube 140 generally acts to protect the wire during delivery and is malleable to allow flexibility without twisting, thereby improving traceability. The hypotube 140 provides rigidity, enabling the torque of the device 102 and ensuring accurate placement of the end effector 114. The hypotube 140 also provides a low-friction outer surface, allowing less force when the outer sheath 138 moves relative to the hypotube 140 during deployment and retraction or restraint. The shaft 116 may be pre-formed in such a manner to complement the nasal cavity. For example, the hypotube 140 may be annealed to produce a bent shaft 116 with a pre-set curve. The hypotube 140 may include, for example, stainless steel tubing that interfacially contacts the liner within the outer sheath 138 for low-friction movement.

[0120] The internal lumen 142 may generally provide a channel for fluid extraction during the treatment procedure. For example, the internal lumen 142 extends from the distal end of the shaft 116 through the hypotube 140 to the atmosphere via a fluid line (line 121 in Figure 4). The internal lumen 142 material is selected to resist the forces of external components acting on it during the procedure.

[0121] Figure 8 is a side view of the handle 118. Figure 9 is a side view of the handle 118 illustrating the internal components enclosed inside. The handle 118 generally includes an ergonomically designed grip portion that provides ambidextrous use for both left-handed and right-handed use, conforms to the anthropometric measurements of the hand, and allows at least one of overhand grip style and underhand grip style during use in procedures. For example, the handle 118 may include specific contours including recesses 144, 146, and 148 that are designed to naturally receive one or more of the operator's fingers in either an overhand grip or underhand grip style and provide a comfortable feel for the operator. For example, in an underhand grip, recess 144 may naturally accommodate the operator's index finger, recess 146 may naturally accommodate the operator's middle finger, recess 148 may naturally accommodate the operator's ring and little fingers (pinkie or pinky) wrapped around the proximal projection 150, and the operator's thumb rests naturally on the upper part of the handle 118 adjacent to the first mechanism 126. In an overhand grip, the operator's index finger may rest naturally on the upper part of the handle 118 adjacent to the first mechanism 126, while recess 144 may naturally accommodate the operator's middle finger, recess 146 may naturally accommodate part of the operator's middle and / or ring fingers, and recess 148 may naturally accommodate and rest inside the space between the operator's thumb and index finger (sometimes referred to as the interdigital space or purlicue).

[0122] As described above, 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 configuration, and a second mechanism 128 for controlling the energy output from the end effector, notably, 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 sufficient distance from each other to allow simultaneous one-handed operation of both user inputs during the procedure. For example, the user input for the first mechanism 126 is positioned on the upper portion of the handle 118 adjacent to the grip portion, and the user input for the second mechanism 128 is positioned on the lateral portion of the handle 118 adjacent to the grip portion. Therefore, in the underhand grip style, the operator's thumb rests on the upper part of the handle adjacent to the first mechanism 126, and at least their middle finger is positioned adjacent to the second mechanism 128, with the first and second mechanisms 126 and 128 being accessible and operable, respectively. In the overhand grip system, the operator's index finger rests on the upper part of the handle adjacent to the first mechanism 126, and at least their thumb is positioned adjacent to the second mechanism 128, with the first and second mechanisms 126 and 128 being accessible and operable, respectively. Thus, the handle adapts to various grip styles, providing a degree of comfort for the surgeon, thereby further improving the execution of the procedure and the overall outcome.

[0123] Referring to Figure 9, various components provided within the handle 118 are illustrated. As shown, the first mechanism 126 may generally include a rack and pinion assembly that provides movement of the end effector 114 between a retracted configuration and an extended 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 linear motion of a rack member 154 operably associated with at least one of the shaft 116 and the end effector 114. The rack and pinion assembly has a gearing ratio sufficient to maintain balance between stroke length and retraction and extension forces, thereby improving control over the extension of the end effector. As shown, the rack member 154 may be coupled to a portion of the shaft 116 such that, for example, movement of the rack member 154 toward the proximal end of the handle 118 results in a corresponding movement of the shaft 116, while the end effector 114 remains stationary, thereby exposing the end effector 114 and allowing it to transition from a constrained retracted configuration to an extended deployed configuration. Similarly, movement of the rack member 154 toward the distal end of the handle 118 results in a corresponding movement of the shaft 116, while the end effector 114 remains stationary, thereby enclosing the end effector 114 within the shaft 116. It should be noted that in other embodiments, the rack member 154 may be directly coupled to a portion of the end effector 114 such that the movement of the rack member 154 results in the corresponding movement of the end effector 114, while the shaft 116 remains stationary, thereby transitioning the end effector 114 between a retracted configuration and an extended configuration.

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

[0125] A user-operated controller associated with the first mechanism 126 can generally provide a high degree of precision and control over the deployment (and retraction) of the first and second segments 122, 124. For example, in some cases, the operator may only want to deploy the second segment 124 during the procedure while the first segment 122 remains in the retracted configuration. The user-operated controller allows the operator to provide sufficient input (i.e., sliding the slider mechanism to a specific position or scrolling the scroll wheel) to transition only the second segment 124 from the retracted configuration to the deployed configuration (while the first segment 122 remains enclosed within the shaft 116 in the retracted configuration). For example, in some embodiments, the end effector 114 may further include a return feature, such as a catch 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 the deployment of the end effector segments and to alert the surgeon when at least the second segment 124 is fully deployed. In particular, as the surgeon slides the slider mechanism or scrolls the scroll wheel during the deployment of the second segment 124, the return feature (provided between the first and second segments 122, 124) may then reach a portion of the shaft 116, causing an increase in resistance on the slider mechanism or scroll wheel, thereby indicating to the surgeon that the second segment 124 has deployed and the first segment 122 remains in the retracted configuration. Thus, the surgeon can position and orient the second segment 124 as desired without concern because the first segment 122 remains in the retracted configuration. Subsequently, once the second segment 124 is positioned at the desired target site, the surgeon may then unfold the first segment 122 and perform the procedure.Furthermore, in some cases, only the second segment 124 may be used to perform the procedure (i.e., to deliver energy to one or more target sites in contact with the second segment 124), and therefore the first segment 122 may never be deployed.

[0126] The second mechanism 128 may generally include a user-operated controller, which is operated between at least an active and inactive position and is configured to control the delivery of energy from the end effector 114, and, notably, the delivery of energy from the electrode 136. The user-operated controller may be multimodal in that it can be operated between multiple positions in which the user-operated controller provides different functions / modes. For example, in response to a single user input (i.e., a single press of a button associated within the controller), the second mechanism may provide a reference juxtaposition / sensing check function prior to modulation. In response to pressing and holding the controller button for a predetermined time period, the energy output from the end effector may be activated. Furthermore, in response to double-tapping the controller button, the energy output may be deactivated.

[0127] Furthermore, the handle and / or shaft may include markings that provide the surgeon with spatial orientation of the end effector while it is in the nasal cavity. Figure 10 is a side view of the handle 118 illustrating multiple markings on the distal end of the handle 118, and Figure 11 is a perspective view of a portion of the shaft 116 illustrating multiple markings on its distal portion. In particular, multiple markings provided on the handle and / or shaft may provide visual indication of the spatial orientation of one or more portions of the first and second segments of the end effector when they are in an unfolded configuration. The markings may include, for example, text, symbols, color-coded marks, or equivalents. Therefore, during the initial placement of the end effector, which is in a retracted configuration and enclosed within the shaft, the surgeon can rely on the handle and / or markings on the shaft as a visual indication of the spatial orientation of the end effector (e.g., linear, axial, and / or depth position) prior to deployment, thereby ensuring that once deployed, the end effector, including both the first and second segments, is positioned in 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 the operator with visual indications of the spatial orientation and architecture resulting from at least the first segment 122 when first navigating the nasal cavity and delivering the distal end of the shaft 116 to the target site prior to the deployment of the end effector 114. In other words, the markings provide the operator with indications of the orientation of at least the first segment 122 of the end effector 114 prior to the deployment of the end effector 114, thereby ensuring accurate positioning at the desired location.

[0129] Figure 12 is a partial sectioned side view illustrating one approach for delivering the 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 within the nasal meatus NP, through the inferior meatus IM between the inferior turbinate IT and the nasal base NS, around the posterior portion of the inferior turbinate IT, where the end effector 114 is deployed at the treatment site. The treatment site may be located in close proximity to one or more access points of postganglionic parasympathetic nerves into the nasal cavity (e.g., posterior nasal nerve branches and / or other parasympathetic nerve fibers distributing nerves to the nasal mucosa). In other embodiments, the target site may be located elsewhere in the nasal cavity, depending on the location of the target nerve.

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

[0131] Furthermore, in further embodiments, the nerve modulation device 102 may be configured for delivery via a guide catheter or an introduction sheath (not shown), with or without the use of a guidewire. The introduction sheath may first be inserted into the lumen to a target site in the nasal region, and the distal portion of the shaft 116 may then be inserted through the introduction sheath. At the target site, the end effector 114 may be deployed through the distal end opening of the introduction sheath or through a side port of the introduction sheath. In some embodiments, the introduction sheath may include a linear portion and a pre-formed portion with a fixed curve (e.g., a 5 mm curve, a 4 mm curve, a 3 mm curve, etc.) that can be deployed into the lumen to access the target site. In this embodiment, the introduction sheath may have a side port proximal to or along the pre-formed curved portion through which the end effector 114 can be deployed. In other embodiments, the introduction sheath may be made from a rigid material, such as a metallic material coated with an insulating or dielectric material. In this embodiment, the inlet sheath is substantially linear and may be used to deliver the end effector 114 to the target site via a substantially linear path, such as through the middle nasal meatus MM (Figure 3A).

[0132] Image guidance may be used to assist the surgeon in positioning and manipulating the distal portion of the shaft 116, and in deploying and manipulating the end effector 114, specifically its first and second segments 122. For example, the endoscope 100 and / or other visualization devices may be positioned during therapeutic neuromodulation to position the target site, the end effector 114 at the target site, and / or visualize the end effector 114. The endoscope 100 may be delivered in close proximity to the target site by extending through the nasal passage NP and through the middle nasal passage MM between the inferior and middle turbinates IT and MT. From a visualization location within the middle nasal passage MM, the endoscope 100 can be used to visualize the treatment site, the surrounding region of the nasal biostructure, and the end effector 114.

[0133] In some embodiments, the distal portion of the shaft 116 may be delivered via a working channel extending through the endoscope, so that the endoscope can provide direct in-line visualization of the target site and the end effector 114. In other embodiments, the endoscope is integrated with the end effector 114 and / or the distal portion of the shaft 116 so as to provide in-line visualization of the end effector 114 and / or surrounding nasal biostructures. In other embodiments, image guidance can be provided using various other guidance modalities such as image filtering in the infrared (IR) spectrum for visualization of the vascular system and / or other anatomical structures, computed tomography (CT), fluoroscopy, ultrasound, optical coherence tomography (OCT), and / or combinations thereof. Furthermore, still in some embodiments, the image guidance component may be integrated with a neuromodulatory device 102 so as to provide image guidance during the positioning of the end effector 114.

[0134] Once positioned at the target site, the therapeutic modulation may be applied to a precisely localized region of the tissue via one or more electrodes 136 and / or other features of the end-effector 114 to induce one or more desired therapeutic modulation effects and interfere with parasympathetic sensorimotor function. The end-effector 114 can selectively target postganglionic parasympathetic nerve fibers that distribute nerves to the nasal mucosa at the target or treatment site, located near or within its entry into the nasal region. For example, the end-effector 114 can be positioned at least near the SPF (Figure 3A) to apply therapeutic neuromodulation and therapeutically modulate nerves entering the nasal region through the SPF. The end-effector 114 can also be positioned below the SPF to apply therapeutic neuromodulation energy across accessory foramina and microforamina (e.g., within the palatine bone) through which the smaller medial and lateral branches of the posterior superior lateral nasal nerve enter the nasal region. The purposeful application of energy at a target site can achieve therapeutic neuromodulation along all or at least some of the posterior nasal nerve fibers entering the nasal region. The therapeutic modulation 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 one embodiment, therapeutic neuromodulation of autonomic nerve fibers is generated by applying RF energy at a power of approximately 2–20 W (e.g., 5 W, 7 W, 10 W, etc.) over a time period of approximately 1–20 seconds (e.g., 5–10 seconds, 8–10 seconds, 10–12 seconds, etc.).

[0135] The therapeutic modulation effect may include partial or complete denervation via thermal ablation and / or non-ablationary thermal modification or damage (e.g., via sustained heating and / or resistance heating). The desired thermal heating effect may include raising the temperature of the target nerve fiber above a desired threshold to achieve non-ablationary thermal modification, or above a higher temperature to achieve ablationary thermal modification. For example, the target temperature may be above body temperature (e.g., about 37°C) but below about 90°C (e.g., 70-75°C) for non-ablationary thermal modification, or the target temperature may be about 100°C or higher (e.g., 110°C, 120°C, etc.) for ablationary thermal modification. The desired non-thermal neuromodulation effect may include modifying the electrical signals transmitted within the nerve.

[0136] Sufficiently modulating at least a portion of the parasympathetic nervous system is expected to slow or potentially block the conduction of autonomic nerve signals to the nasal mucosa, resulting in a long-term or permanent reduction of nasal parasympathetic activity. This is expected to reduce or eliminate submucosal gland activation or hyperactivation and venous congestion, thereby reducing or eliminating the symptoms of rhinosinusitis. Furthermore, because device 102 applies therapeutic neuromodulation to multiple posterior nasal nerve branches rather than a single large branch of the posterior nasal nerve branches entering the nasal cavity in the SPF, device 102 provides a more complete disruption of the parasympathetic pathway that affects the nasal mucosa and leads to rhinosinusitis. Therefore, device 102 is expected to improve the therapeutic effect for the treatment of rhinosinusitis and reduce reinnervation of the treated mucosa.

[0137] In other embodiments, device 102 may be configured to therapeutically modulate nerves and / or other structures to treat different indications. For example, device 102 may be used to therapeutically modulate nerves that supply nerves to the sinuses to treat chronic sinusitis. In further embodiments, system 100 and device 102 disclosed herein may be configured to therapeutically modulate the vascular system within the nasal biostructure to treat other indications such as epistaxis (i.e., excessive bleeding from the nose). For example, system 100 and device 102 described herein may be used to apply therapeutically effective energy to arteries (e.g., sphenopalatine arteries and their branches) as they enter the nasal cavity (e.g., via SPF, accessory foramina, etc.) to partially or completely coagulate or ligate the arteries. In other embodiments, system 100 and device 102 may be configured to partially or completely coagulate or ligate veins and / or other blood vessels. In embodiments in which the end effector 114 ligates or coagulates the vascular system, the system 100 and device 102 would be modified to deliver energy at a significantly higher power (e.g., about 100 W) and / or for a longer duration (e.g., 1 minute or longer) than would be required for therapeutic neuromodulation.

[0138] Figure 13 is a flowchart illustrating one embodiment of Method 400 for treating a patient's nasal cavity condition. Method 400 includes the step (operation 410) of advancing a multi-segment end-effector into the patient's nasal cavity, the multi-segment end-effector including a first segment separated from a second segment. Once delivered to one or more target sites in the nasal cavity, the multi-segment end-effector is retractable and expandable so that the first and second segments can expand to a specific shape and / or size corresponding to the anatomical structures associated with the nasal cavity and the target sites. Method 400 further includes the step (operation 420) of deploying the first and second segments at separate first and second locations in the nasal cavity. In particular, the first and second flexible segments each include a specific geometric shape to complement the biostructure of the separate location in the nasal cavity when in the deployed configuration. Therefore, once deployed, the first and second segments include conforming to and complementing the shape of one or more anatomical structures at individual locations, contacting and conforming to the shape of individual locations. Method 400 further includes the step (operation 430) of delivering energy to tissue at one or more target sites relative to the first and second locations via the first and second segments. In particular, the first and second segments are positioned precisely within the nasal cavity, and subsequently, a precise focused application of RF thermal energy is delivered to one or more target sites via one or more electrodes, thereby therapeutically modulating the associated nerve structures. When in an extended configuration, the first and second segments have shapes and sizes specifically designed to position portions of the first and second segments, and therefore one or more electrodes associated with them, in contact with target sites within the nasal cavity associated with postganglionic parasympathetic nerve fibers distributing nerves to the nasal mucosa.

[0139] Figure 14 is a flowchart illustrating another embodiment of Method 500 for treating a patient's nasal cavity condition. Method 500 includes the step (operation 510) of providing a therapeutic device comprising an end effector convertible between a retracted configuration and an extended configuration, a shaft operably associated with the end effector, and a handle operably associated with the shaft. Method 500 further includes the step (operation 520) of advancing the end effector to one or more target sites in the patient's nasal cavity. The shaft may include a predetermined shape (i.e., bent or angled in a specific orientation) to assist in the operation for setting the end effector at the target site. The handle includes an ergonomically designed grip portion that provides ambidextrous use for both left-handed and right-handed use, conforms to the anthropometric measurements of the hand, and allows at least one of an overhand grip style and an underhand grip style during use in the procedure.

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

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

[0142] Figure 15 is a flowchart illustrating another embodiment of Method 600 for treating a patient's nasal cavity condition. Method 600 includes the step (operation 610) of providing a therapeutic device comprising a multi-segment end effector including a proximal segment spaced apart from a distal segment and a visual marker. As described above herein, the visual marker may be provided, for example, by a shaft operably associated with the multi-segment end effector. The visual marker may be in the form of text, symbols, color markings, or equivalents, generally providing 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 while the multi-segment end effector is in the nasal cavity.

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

[0144] Depending on the deployment of the distal segment to an extended configuration, Method 600 further includes the step (operation 640) of aligning the proximal segment with respect to the middle concha, with reference to a visual marker under image guidance. The visual marker is provided on the shaft and may provide visual indication of the spatial orientation of one or more parts of the proximal segment when it is in an extended configuration, for example. For example, the deployed proximal segment may include geometric shapes to complement the shape of the middle concha. More specifically, the proximal segment may include a set of flexible support elements that conform to and complement the shape of the middle concha when the proximal segment is in an extended configuration. The visual marker provided by the shaft provides visual indication of the spatial orientation of one or more parts of the proximal segment, including, for example, the spatial orientation of the set of flexible support elements when it is in an extended configuration. Thus, the step of aligning the proximal segment with respect to the middle concha includes the step of the user positioning the shaft and associated visual markers with respect to the middle concha when it is in an extended configuration.

[0145] Therefore, at least during the initial placement of the proximal segment, when it is 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 its deployment, thereby ensuring that once deployed, the proximal segment is positioned in its intended location within the nasal cavity.

[0146] Method 600 further includes the step (action 650) of unfolding the proximal segment around the middle turbinate, advancing the unfolded proximal segment toward the middle turbinate to establish contact and fix the proximal segment to the middle turbinate. Again, the set of flexible support elements of the proximal segment conforms to and complements the shape of the middle turbinate when the proximal segment is in an unfolded extended configuration, thereby ensuring that the unfolded proximal segment is fixed to the middle turbinate.

[0147] It should be noted that the therapeutic device further includes a multi-segment end effector and a handle operably associated with the shaft. The handle generally includes a controller mechanism for providing independently controlled deployment of the proximal and distal segments from a retracted configuration to an extended 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 and distal segments between the retracted and extended configurations 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 a user-operated controller and converting the user input into linear motion of a rack member operably associated with the multi-segment end effector.

[0148] The controller mechanism may further include a stopper feature positioned relative to the proximal and distal segments and configured to provide the user with active feedback indicating the deployment of at least one of the proximal and distal segments. The active feedback may take the form of haptic feedback provided by the controller mechanism. For example, the haptic feedback may include an increase or decrease in resistance associated with user input, using the controller mechanism for the corresponding movement of at least one of the proximal and distal segments between a retracted configuration and an extended configuration, and / or configurations in between (i.e., multiple configurations between a fully retracted configuration and a fully extended configuration). For example, in response to the deployment of the distal segment, the controller mechanism may, as a result of interaction with the stopper, provide the user with haptic feedback in the form of vibration or other motion (e.g., a click or a change in resistance) via a user-operated controller. The haptic feedback may indicate to the user that the distal segment is fully deployed, and any further input using the user-operated controller would result in the deployment of the proximal segment. The controller mechanism may further provide specific haptic feedback during the deployment of a given segment, such as the deployment of the proximal segment. For example, haptic feedback may take the form of increasing or decreasing resistance on a user-operated controller, corresponding to, for instance, the degree to which a proximal segment is unfolded.

[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 and distal segments between a retracted configuration and an extended configuration, and further to provide the user with active feedback indicating the deployment of at least one of the proximal and distal segments. The friction-based feature may include, for example, a locking mechanism configured to provide constant friction between one or more parts of a rack and pinion assembly, which is sufficient to maintain the position of at least one of the proximal and distal segments during its deployment.

[0150] For example, a certain amount of friction may be sufficient to hold either the proximal or distal segment in place as the segment transitions between a retracted and extended configuration, regardless of whether the user maintains contact with the user-operated controller. In other words, the user does not need to maintain contact with the user-operated controller to ensure that the proximal or distal segment holds its position during its deployment. Rather, the user can simply interact with the user-operated controller and transition one of the proximal and distal segments to the desired configuration, and the constant friction provided by the locking mechanism is sufficient to maintain the configuration of the proximal or distal segment when the user has both hands free (i.e., removes any contact with the user-operated controller). The constant friction is still at a level sufficient to prevent undesirable movement of the proximal or distal segment (i.e., unintended crushing or expansion), while allowing the user to overcome such friction and move the proximal or distal segment to the desired configuration in response to user input using the user-operated controller.

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

[0152] Therefore, during the deployment of either the distal or proximal segment, the controller mechanism provides active feedback to the user, such active feedback indicating the degree of deployment of the actively controlled segment and / or either the distal or proximal segment, thereby improving user control over the deployment of either the distal or proximal segment.

[0153] Depending on the fixation of the proximal segment to the middle turbinate, Method 600 further includes the step (operation 660) of delivering energy to the middle turbinate via the proximal segment to treat a 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, as well as combinations thereof. In some embodiments, the step of delivering energy from the proximal segment includes the step of delivering radio frequency (RF) energy to the tissue of the middle turbinate at one or more target sites via one or more electrodes provided by the proximal segment, where one or more target sites are associated with parasympathetic nerve supply. In some embodiments, the RF energy is delivered via one or more electrodes provided by the proximal segment to a level sufficient to therapeutically modulate the postganglionic parasympathetic nerves that distribute nerves to the nasal mucosa in the nerve supply pathways within the patient's nasal cavity.

[0154] Therefore, the handheld device of the present invention provides a user-friendly, non-invasive means for treating rhinosinusitis conditions, including the precise focused application of RF thermal energy to a intended target site for therapeutic modulation of the intended nerve structure, without causing incidental, unintended damage or interference to other nerve structures. Thus, the effectiveness of the Vidian nerve sectioning procedure can be achieved using the system and method of the present invention without the drawbacks discussed above. Most notably, the handheld device provides surgeons with a user-friendly, non-invasive, and precise means for treating such conditions by targeting only those specific nerve structures associated with rhinorrhea and other symptoms of rhinosinusitis, namely the postganglionic parasympathetic nerves distributing nerves to the nasal mucosa, thereby disrupting the parasympathetic supply and blocking parasympathetic tension. Therefore, such treatment is effective in treating rhinosinusitis conditions while greatly reducing the risk of incidental damage or interference to other nerve fibers, thereby reducing the possibility of unintended complications and side effects. (Neuromodulation monitoring, feedback, and mapping capabilities)

[0155] As described above, the system 100 includes a console 104 to which the device 102 will be connected. The console 104 is configured to provide various functions for the neuromodulatory device 102, which may include, but are not limited to, control, monitor, supply, and / or otherwise support operations for the neuromodulatory device 102. The console 104 may further be configured to generate energy of a selected form and / or magnitude for delivery to tissue or nerve at a target site via the end effector 114, and therefore the console 104 may have different configurations depending on the therapeutic modality of the device 102. For example, when device 102 is configured for electrode-based, thermal element-based, and / or transducer-based therapy, console 104 includes an energy generator 106 configured to generate RF energy (e.g., unipolar, bipolar, or multipolar RF energy), pulsed electrical energy, microwave energy, optical energy, ultrasonic energy (e.g., intraluminal ultrasound and / or HIFU), direct thermal energy, radiation (e.g., infrared, visible, and / or gamma radiation), and / or another preferred type of energy. When device 102 is configured for cryotherapy therapy, console 104 may include a refrigerant reservoir (not shown) and may be configured to supply refrigerant to device 102. Similarly, when device 102 is configured for chemical-based therapy (e.g., drug infusion), console 104 may include a chemical reservoir (not shown) and may be configured to supply one or more chemicals to device 102.

[0156] In some embodiments, the console 104 may include a controller 107 that is communicatively coupled to the neuromodulatory device 102. However, in the embodiments described herein, the controller 107 may generally be carried by a handle 118 of the neuromodulatory device 102 and provided inside it. The controller 107 is configured to start, stop, and / or adjust the operation of one or more electrodes provided by the end effector 114, directly and / or via the console 104. For example, the controller 107 may be configured to execute an automatic control algorithm and / or to receive control commands 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, when executed by the controller 107, carries commands, carries commands, and causes the device 102 to perform functions (e.g., apply energy in a specific manner, detect impedance, detect temperature, detect nerve location or anatomical structure, perform nerve mapping, etc.). Memory includes one or more hardware devices for volatile and non-volatile storage, and can include both read-only and writable memory. For example, memory can 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, and device buffers. Memory is not a propagating signal isolated from the underlying hardware, and therefore memory is non-transient.

[0157] Console 104 may further be configured to provide feedback to the operator before, during, and / or after a therapeutic procedure via a mapping / evaluation / feedback algorithm 110. For example, the mapping / evaluation / feedback algorithm 110 may 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 modulation, and / or the effect of therapeutic neuromodulation on nerves at the treatment site. In some embodiments, the mapping / evaluation / feedback algorithm 110 may include features to confirm the effectiveness of the therapy and / or improve the desired performance of the system 100. For example, the mapping / evaluation / feedback algorithm 110, in conjunction with the controller 107 and end effector 114, may be configured to monitor nerve activity and / or temperature at the treatment site during therapy and to automatically stop energy delivery when nerve activity and / or temperature reach predetermined thresholds (e.g., threshold reduction of nerve activity, threshold maximum temperature when RF energy is applied, or threshold minimum temperature when cryotherapy is applied). In other embodiments, the mapping / evaluation / feedback algorithm 110, in conjunction with the controller 107, may be configured to automatically terminate treatment after a predetermined maximum time, a predetermined maximum impedance or resistance rise of the target tissue (i.e., compared to a reference impedance measurement), a predetermined maximum impedance of the target tissue, and / or other thresholds relating to biomarkers associated with autonomous functions. Book and other information associated with the operation of the system 100 may be communicated to the operator via a display 112 on the console 104 (e.g., a monitor, touchscreen, user interface, etc.) and / or a separate display (not shown) communicably coupled to the console 104.

[0158] In various embodiments, the end effector 114 and / or other parts of the system 100 may be configured to detect various bioelectrical parameters of tissue at a target site, and this information may be used by the mapping / evaluation / feedback algorithm 110 to determine biostructure (e.g., tissue type, tissue location, vascular system, bone structure, foramen, sinuses, etc.) at the target site, identify nerve structures, distinguish between different types of nerve structures, map anatomical and / or nerve structures at the target site, and / or identify the neuromodulation pattern of the end effector 114 on the patient's biostructure. For example, the end effector 114 may be used to detect resistance, complex electrical impedance, dielectric properties, temperature, and / or other properties indicating the presence of nerve fibers and / or other anatomical structures within the target region. In some embodiments, the end effector 114 may be used in conjunction with the mapping / evaluation / feedback algorithm 110 to determine the resistance (rather than impedance) of tissue (i.e., load) to more accurately identify the characteristics of the tissue. The mapping / evaluation / feedback algorithm 110 can determine the tissue's resistance by detecting the actual power and current of the load (for example, via the electrode 136).

[0159] In some embodiments, System 100 provides resistance measurement with high accuracy and very high precision, such as measurement accuracy down to 1 / 100th of an ohm (e.g., 0.01 W) in the range of 1 to 50 W. The high resistance detection accuracy provided by System 100 enables the detection of submicroscale structures, including the firing of nerve structures, differences between nerve structures and other anatomical structures (e.g., blood vessels), and even different types of nerve structures. This information can be analyzed by a mapping / evaluation / feedback algorithm and / or controller 107 and communicated to the operator via a high-resolution spatial grid and / or other type of display (e.g., on display 112) to identify nerve structures and other biostructures at the treatment site, and / or indicate predicted neuromodulation areas based on ablation patterns on the mapped biostructures.

[0160] As described above, 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 a control algorithm performed by an operator or controller 107. Selective independent control of the electrodes 136 allows the end effector 114 to detect information and deliver RF energy to highly customized areas. For example, a selected portion of electrode 136 can be activated to target specific nerve fibers within a specific region, while other electrodes 136 remain inactive. In some embodiments, for example, electrode 136 may be activated across a portion of a second segment 124 adjacent to tissue at the target site, while electrodes 136 not adjacent to the target tissue remain inactive, avoiding the application of energy to non-target tissue. In addition, electrodes 136 can be individually activated (e.g., via multiplexing) to stimulate or therapeutically modulate specific patterns of regions at different times, thereby facilitating the detection of anatomical parameters across the zone of interest and / or tuned therapeutic neuromodulation.

[0161] Electrodes 136 can be electrically coupled to the energy generator 106 via wires (not shown) extending from the electrodes 136 through the shaft 116 to the energy generator 106. When each electrode 136 is controlled independently, each electrode 136 is coupled to a corresponding wire extending through the shaft 116. This allows each electrode 136 to be activated independently for stimulation or neuromodulation, providing a precise ablation pattern, and / or individually detected via the console 104, providing information specific to each electrode 136 for neurological or anatomical detection and mapping. In other embodiments, multiple electrodes 116 can be controlled together, and therefore multiple electrodes 116 can be electrically coupled to the same wire extending through the shaft 116. The energy generator 16 and / or components operably coupled to it (e.g., a control module) may include custom algorithms for controlling the activation of the electrodes 136. For example, the RF generator can deliver RF power in the range of approximately 200–100W to the electrode 136, activating the electrode 136 in a predetermined pattern selected based on the position of the end effector 114 relative to the treatment site and / or identified location of the target nerve. In other embodiments, the energy generator 106 delivers power at lower levels (e.g., less than 1W, 1–5W, 5–15W, 15–50W, 50–150W, etc.) and / or higher power levels for stimulation. For example, the energy generator 106 can be configured to deliver a stimulating energy pulse of 1–3W via the electrode 136 to stimulate a specific target within the tissue.

[0162] As described above, the end effector 114 may further include one or more temperature sensors positioned on the flexible first and second segments 122, 124 and / or other parts of the end effector 114 and electrically coupled to the console 104 via wires (not shown) extending through the shaft 116. In various embodiments, the temperature sensors may be positioned close to the electrode 136 to detect the temperature at the interface between the tissue and the electrode 136 at the target site. In other embodiments, the temperature sensors may penetrate the tissue at the target site (e.g., through-hole thermocouple) and detect the temperature at some depth within the tissue. Temperature measurements can provide feedback to the operator or system regarding the effects of therapeutic neuromodulation on the tissue. For example, in one embodiment, the operator may desire to prevent or reduce damage to tissue (e.g., nasal mucosa) at the treatment site, and therefore the temperature sensors may be used to determine whether the tissue temperature has reached a predetermined threshold for irreversible tissue damage. Once a threshold is reached, the application of therapeutic neuromodulation energy can be terminated to allow the tissue to remain intact and avoid significant tissue loss during wound healing. In one embodiment, energy delivery can be automatically terminated based on a mapping / evaluation / feedback algorithm 110 stored on a console 104 operably coupled to a temperature sensor.

[0163] In some embodiments, the system 100 can determine the location and / or morphology of nerve structures and / or other anatomical structures before therapy so that therapeutic neuromodulation can be applied to a precise area including target nerve structures, while avoiding adverse effects on non-target structures such as blood vessels. As will be described in more detail below, the system 100 can detect various bioelectrical parameters within the zone of interest (e.g., within the nasal cavity) and determine the location and morphology of various nerve structures (e.g., different types of nerve structures, nerve directivity, 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 do so, one or more of the electrodes 136 are placed in contact with the epithelial surface in the area of ​​interest (e.g., treatment site). Electrical stimulation (e.g., a constant or pulsed current at one or more frequencies) is applied to tissue by one or more electrodes 136 at or near the treatment site, and voltage and / or current differences at various different frequencies between various pairs of electrodes 136 of the end effector 114 may be measured to generate a spectral profile or map of detected biopotentials, which can be used to identify different types of tissue within the region of interest (e.g., blood vessels, nerve structures, and / or other types of tissue). For example, a current (i.e., DC or AC) can be applied to a pair of electrodes 136 adjacent to each other, and the resulting voltage and / or current between other pairs of adjacent electrodes 136 is measured. It should be understood that the current injection electrodes 136 and the measurement electrodes 136 do not need to be adjacent, and modifying the spacing between the two current injection electrodes 136 may affect the depth of the recorded signal. For example, closely spaced current injection electrodes 136 provided recorded signals associated with tissue at shallower depths, while more widely spaced current injection electrodes 136 provided recorded signals associated with tissue deeper from the tissue surface. Recordings from electrode pairs with different spacings may be merged to provide additional information about the depth and location of anatomical structures.

[0164] Furthermore, while complex impedance and / or resistance measurements of tissue in the region of interest can be directly detected from current-voltage data provided by biopotential measurements, different levels of frequency currents can be applied to the tissue (e.g., via end effector 114), and this information can be used to map nerve and anatomical structures by using frequency differential reconstruction. Applying stimuli at different frequencies will target different stratified layers or cell bodies or groups. At high signal frequencies (e.g., electrical injection or stimulation), for example, the cell membrane of a nerve structure does not obstruct the flow of current, and the current passes directly through the cell membrane. In this case, the resulting measurements (e.g., impedance, resistance, capacitance, and / or induction) are functions of intracellular and extracellular tissue as well as fluid. At low signal frequencies, the membrane obstructs the flow of current, providing different definitive characteristics of the tissue, such as cell morphology or cell spacing. The stimulation frequency may be in the megahertz range, the kilohertz range (e.g., 400-500 kHz, 450-480 kHz, etc.), and / or other frequencies that are tuned to the characteristics of the tissue being stimulated and the device being used. The complex impedance or resistance level detected from the zone of interest may be displayed to the user (e.g., via display 112) to visualize a certain structure based on the stimulation frequency.

[0165] Furthermore, the unique morphology and composition of anatomical structures within the nasal region may respond differently to different frequencies, and therefore, specific frequencies can be selected to identify highly specific structures. For example, the morphology or composition of a target structure for anatomical mapping may depend on whether the cells or other structures of the tissue are membranous, stratified, and / or annular. In various embodiments, the applied stimulus signal may have predetermined frequencies that are tuned to specific nerve structures, such as the level of myelination and / or the morphology of myelination. For example, a second axonal parasympathetic nerve structure may be less myelinated than a sympathetic nerve or other structure, and therefore have a more distinguishable response (e.g., complex impedance, resistance, etc.) to selected frequencies than the sympathetic nerve. Thus, applying signals with different frequencies to a target site can distinguish the target parasympathetic nerve from the non-target sensory nerve, and therefore provide highly specific target sites for pre- or post-therapy nerve mapping and / or post-therapy nerve evaluation. In some embodiments, nerve and / or anatomical mapping includes the step of identifying a certain anatomical structure by measuring data in a region of interest using at least two different frequencies, such that the measurement is obtained first based on the response to an injection signal having a first frequency, and then again based on an injection signal having a second frequency different from the first frequency. For example, there are two frequencies in which a hypertrophied (i.e., disease-state-characterized) submucosal target has different electrical conductivity or dielectric constant compared to “normal” (i.e., healthy) tissue. Complex conductivity may be determined based on observation of one or more measured physiological parameters (e.g., complex impedance, resistance, dielectric measurement, dipole measurement, etc.) and / or one or more confidently known attributes or signatures. Furthermore, system 100 can also apply neuromodulation energy via electrode 136 at one or more predetermined frequencies tuned to the target nerve structure, providing highly targeted ablation of selected nerve structures associated with the frequency.This highly targeted neuromodulation also reduces the cascading effects of neuromodulation therapy on non-target sites / structures (e.g., blood vessels), because the target signal (having a frequency tuned to the target neural structure) will not exert the same modulation effect on non-target structures.

[0166] Therefore, bioelectrical properties such as complex impedance and resistance can be used by System 100 before, during, and / or after neuromodulation therapy to induce one or more therapeutic parameters. For example, before, during, and / or after treatment, impedance or resistance measurements may be used to confirm and / or detect contact between one or more electrodes 136 and adjacent tissue. Impedance or resistance measurements may also be used to detect whether electrodes 136 are properly positioned for the target tissue type by determining whether the recorded spectrum has a shape that matches the expected tissue type and / or whether the continuously collected spectra were reproducible. In some embodiments, impedance or resistance measurements may be used to identify boundaries for the treatment zone (e.g., specific nerve structures to be disturbed), anatomical landmarks, anatomical structures to be avoided (e.g., vascular or nerve structures that should not be disturbed), and other aspects of delivering energy to the tissue.

[0167] Bioelectrical information can be used to generate a spectral profile or map of tissue with different anatomical features at a target site, and the anatomical mapping can be visualized in 3D or 2D images via display 112 and / or other user interfaces to guide the selection of a suitable treatment site. This nerve and anatomical mapping enables system 100 to accurately detect and therapeutically modulate postganglionic parasympathetic nerve fibers that distribute nerves to the mucosa at numerous nerve entry points into the nasal cavity. Furthermore, since there are no clear anatomical markers indicating the location of SPFs, accessory foramina, and micropores, nerve mapping enables the operator to identify and therapeutically modulate nerves that would otherwise be indistinguishable without complex mucosal dissection. In addition, anatomical mapping also enables clinicians to identify certain structures (e.g., certain arteries) that they may wish to avoid during therapeutic neuromodulation. The nerve and anatomical bioelectrical properties detected by system 100 can also be used during and after treatment to determine the real-time effect of therapeutic neuromodulation on the treatment site. For example, the mapping / evaluation / feedback algorithm 110 can also compare detected neuronal locations and / or activity before and after therapeutic neuromodulation, compare changes in neuronal activity to predetermined thresholds, and assess whether the application of therapeutic neuromodulation was effective across the treatment site.

[0168] In various embodiments, the system 100 may also be configured to map the expected therapeutic modulation pattern of the electrode 136 at specific temperatures, and in some embodiments, to take tissue properties into account based on an anatomical mapping of the target site. For example, the system 100 may be configured to map the ablation pattern of a specific electrode ablation pattern at 45°C isotherms, 55°C isotherms, 65°C isotherms, and / or other temperature / ranges (e.g., temperatures ranging from 45°C to 70°C or higher), depending on the target site and / or structure.

[0169] System 100 may provide a three-dimensional view of such projected ablation patterns of electrodes 136 of end effector 114 via display 112. Ablation pattern mapping may define the area of ​​influence each electrode 136 has on the surrounding tissue. The area of ​​influence may correspond to the area of ​​tissue that will be exposed to therapeutic modulation energy based on a defined electrode activation pattern (i.e., one, two, three, four, or more electrodes on any given support of the first and second segments 122, 124). In other words, ablation pattern mapping can be used to illustrate the ablation patterns of any number of electrodes 136, any geometric shape of the electrode layout, and / or any ablation activation protocol (e.g., pulsed activation, multi-pole / continuous activation, etc.).

[0170] In some embodiments, the ablation pattern may be configured such that each electrode 136 has an area of ​​influence (i.e., a "dot" pattern) surrounding only the individual electrode 136. In other embodiments, the ablation pattern may be such that two or more electrodes 136 link together and form subgrouped areas of influence defining a peanut-like or linear shape between the two or more electrodes 136. In further embodiments, the ablation pattern may result in a broader or adjacent pattern in which the areas of influence extend along multiple electrodes 136 (e.g., along each support). In even further embodiments, the ablation pattern may result in different areas of influence depending on the electrode activation pattern, phase angle, target temperature, pulse duration, device structure, and / or other therapeutic parameters. A three-dimensional view of the ablation pattern can be output to display 112 and / or other user interfaces to enable clinicians to visualize areas of influence that vary based on different durations of energy application, 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 the patient's specific biostructure. In other embodiments, the three-dimensional visualization of the areas of influence can be used to illustrate the areas where electrodes 136 detect data when measuring bioelectrical properties with respect to anatomical mapping. In this embodiment, the three-dimensional visualization can be used to determine an electrode activation pattern that should be used to determine a desired property (e.g., impedance, resistance, etc.) within a desired area. In some embodiments, dot assessment may be better, while in other embodiments, it may be better to detect information from linear or larger adjacent areas.

[0171] In some embodiments, the mapped ablation pattern is overlaid on an anatomical map to identify types of structures (e.g., nerve structures, blood vessels, etc.) that will be therapeutically modulated or otherwise affected by the therapy. Images, including a digital diagram of the predicted or planned neuromodulation zone in relation to pre-identified anatomical structures within the zone of interest, may be provided to the surgeon. For example, the diagram may show a number of nerve structures and identify the nerve structures expected to be therapeutically modulated based on the predicted neuromodulation zone. The expected therapeutically modulated nerve structures may be shaded to distinguish them from unaffected nerve structures. In other embodiments, the expected therapeutically modulated nerve structures can be distinguished from unaffected nerve structures using different colors and / or other indicators. In further embodiments, the predicted neuromodulation zone and surrounding biostructures (based on the anatomical map) may be shown in a three-dimensional view and / or include different visualization features (e.g., color coding to identify certain anatomical structures, bioelectrical properties of target tissue, etc.). The combined predicted ablation patterns and anatomical mappings can be output to display 112 and / or other user interfaces to enable clinicians to select an appropriate ablation algorithm for the patient's specific biological structure.

[0172] The imaging provided by System 100 allows clinicians to visualize the ablation pattern before treatment, adjust the ablation pattern, target specific anatomical structures while avoiding others, and prevent adverse effects. For example, clinicians can select a treatment pattern to avoid blood vessels, thereby reducing their exposure to therapeutic neuromodulation energy. This reduces the risk of damaging or rupturing blood vessels and thus prevents immediate or latent bleeding. Furthermore, the selective energy application provided by nerve mapping reduces adverse effects of therapeutic neuromodulation, such as tissue shedding during wound healing (e.g., 1-3 weeks after ablation), thereby reducing the risk of aspiration associated with neuromodulation procedures.

[0173] System 100 can further be configured to apply neuromodulation energy (via electrode 136) at a specific frequency tuned to the target neural structure, and thus specifically target the desired neural structure compared to non-target structures. For example, the specific neuromodulation frequency may correspond to a frequency identified as corresponding to the target structure during neuromapping. As described above, the intrinsic morphology and composition of anatomical structures respond differently to different frequencies. Therefore, frequency-tuned neuromodulation energy matched to the target structure will not exert the same modulation effect on non-target structures. More specifically, applying neuromodulation energy at a target-specific frequency causes ion agitation within the target neural structure, leading to differences in the osmotic potential and dynamic changes in the nerve membrane potential (due to differences in intracellular and extracellular fluid pressure). This causes degeneration, potentially leading to vacuolar degeneration and ultimately necrosis in the target neural structure, but is not expected to functionally affect at least some non-target structures (e.g., blood vessels). Therefore, system 100 can use neural structure-specific frequencies to (1) identify the location of target neural structures for planning electrode ablation configurations (e.g., electrode geometry and / or activation patterns) that specifically focus neuromodulation onto the target neural structures, and (2) apply neuromodulation energy at characteristic neural frequencies to selectively ablate neural structures in response to those characteristic neural frequencies. For example, the end effector 114 of system 100 may selectively stimulate and / or modulate parasympathetic fibers, sympathetic fibers, sensory fibers, alpha / beta / delta fibers, C-fibers, anaerobic terminals of one or more of the aforementioned, insulating fibers (regions with fibers) compared to non-insulated fibers, and / or other neural structures. In some embodiments, system 100 may also selectively target specific cells or cell regions, such as smooth muscle cells, submucosal glands, goblet cells, or stratified cell regions within the nasal mucosa, during anatomical mapping and / or therapeutic modulation.Therefore, system 100 provides highly selective neuromodulation therapy specific to the target neural structure, reducing the adverse effects of neuromodulation therapy on non-target structures (e.g., blood vessels).

[0174] This disclosure provides methods for anatomical mapping and therapeutic neuromodulation. The method includes the step of extending an end effector (i.e., end effector 114) in a zone of interest ("zone of interest"), such as within a portion of the nasal cavity. For example, the end effector 114 can be extended so that at least some of the electrodes 136 are positioned in contact with mucosal tissue in the zone of interest. The extended device can then perform bioelectrical measurements via the electrodes 136 and / or other sensors to ensure that the desired electrodes are in proper contact with the tissue in the zone of interest. In some embodiments, for example, system 100 detects impedance and / or resistance across pairs of electrodes 136 to confirm that the desired electrodes have proper surface contact with the tissue and that all of the electrodes 136 are functioning properly.

[0175] This method optionally involves applying electrical stimulation to tissue, detecting the bioelectrical properties of the tissue, and establishing a reference norm for the tissue. For example, the method may include steps of measuring resistance, complex impedance, current, voltage, nerve firing rate, nerve magnetic field, muscle activation, and / or other parameters indicating the location and / or function of nerve structures and / or other anatomical structures (e.g., glandular structures, blood vessels, etc.). In some embodiments, electrode 136 transmits one or more stimulation signals (e.g., pulsed signals or constant signals) to the zone of interest, stimulating nerve activity and initiating an action potential. The stimulation signals may have frequencies that are tuned to specific target structures (e.g., specific nerve structures, glandular structures, blood vessels) that allow for the identification of the location of specific target structures. The specific frequency of the stimulation signal is a function of host penetration; therefore, applying a unique frequency modifies tissue attenuation and the depth into the tissue that the RF energy will penetrate. For example, lower frequencies typically penetrate deeper into the tissue than higher frequencies.

[0176] A pair of non-stimulating electrodes 136 of the end effector 114 can then detect one or more bioelectrical properties of tissue that arise in response to a stimulus, such as impedance or resistance. For example, an array of electrodes (e.g., electrodes 136) can be selectively paired together in a desired pattern (e.g., multiplexing electrodes 136) to detect bioelectrical properties at a desired depth and / or across a desired region, providing a high level of spatial recognition in the zone of interest. In some embodiments, the electrodes 136 can be paired together in a time-series manner according to an algorithm (e.g., provided by a mapping / evaluation / feedback algorithm 110). In various embodiments, stimuli can be injected into the tissue at two or more different frequencies, and the resulting bioelectrical responses (e.g., action potentials) in response to each of the injected frequencies can be detected via various pairs of electrodes 136. For example, an anatomical or neural mapping algorithm can cause the end effector 114 to deliver pulsed RF energy at specific frequencies between different pairs of electrodes 136, and the resulting bioelectrical responses can be recorded in chronological order until the desired zone of interest is properly mapped (i.e., "multiplexed"). For example, the end effector 114 can deliver stimulating energy at a first frequency over a predetermined time period (e.g., 1 to 50 milliseconds) via adjacent pairs of electrodes 136, and the resulting bioelectrical activity (e.g., resistance) can be detected via one or more other pairs of electrodes 136 (e.g., spaced apart to reach varying depths within the tissue). The end effector 114 can then apply stimulating energy at a second frequency different from the first frequency, and the resulting bioelectrical activity can be detected via the other electrodes. This can be continued when the zone of interest is properly mapped at the desired frequency. As will be described in more detail below, in some embodiments, the bioelectrical properties of a reference tissue (e.g., nerve firing rate) are detected using a static detection method (without the injection of a stimulus signal).

[0177] After detecting reference bioelectrical properties, the information can be used to map anatomical structures and / or functions in the zone of interest. For example, bioelectrical properties detected by electrode 136 can be analyzed via mapping / evaluation / feedback algorithm 110, and the anatomical map can be output to the user via display 112. In some embodiments, complex impedance, dielectric, or resistance measurements can be used to map parasympathetic nerves and, optionally, to identify nerve structures in hyperactive pathological states. Bioelectrical properties can also be used to map other non-target structures such as blood vessels, bones, and / or glandular structures, as well as general biostructures. Anatomical locations can be provided to the user (e.g., on display 112) as a two-dimensional map (e.g., illustrating relative intensity, illustrating specific locations of potential target structures) and / or as a three-dimensional image. This information can be used to differentiate structures at the submicron cellular level and identify very specific target structures (e.g., hyperactive parasympathetic nerves). This method can also predict the ablation pattern of the end effector 114 based on different electrode neuromodulation protocols and optionally superimpose the predicted neuromodulation pattern onto mapped biostructures to show the user the anatomical structures that would be affected by a specific neuromodulation protocol. For example, when the predicted neuromodulation pattern is displayed in relation to the mapped biostructure, a clinician can determine whether the target structure will be ablated appropriately and whether non-target structures (e.g., blood vessels) will be undesirably exposed to the therapeutic neuromodulation energy. Therefore, this method can be used to plan neuromodulation therapy, identify very specific target structures, avoid non-target structures, and select electrode neuromodulation protocols.

[0178] Once a target structure is identified and a desired electrode neuromodulation protocol is selected, the method continues by applying therapeutic neuromodulation to the target structure. The neuromodulation energy can be applied to the tissue in a highly targeted manner, selectively modulating the target structure and forming microlesions while avoiding non-target blood vessels and allowing surrounding tissue structures to remain healthy for effective wound healing. In some embodiments, the neuromodulation energy can be applied in pulsed form, allowing the tissue to cool between modulation pulses and ensuring proper modulation without undesirable effects on non-target tissue. In some embodiments, the neuromodulation algorithm can deliver pulsed RF energy between different pairs of electrodes 136 in a time-series sequence until neuromodulation is expected to be complete (i.e., "multiplexed"). For example, the end effector 114 can deliver neuromodulation energy (e.g., having a power of 5-10W (e.g., 7W, 8W, 9W) and a current of about 50-100mA) through the adjacent pair of electrodes 136 until at least one of the following conditions is met: (a) the load resistance reaches a predetermined maximum resistance (e.g., 350W), (b) the thermocouple temperature associated with the electrode pair reaches a predetermined maximum temperature (e.g., 80°C), or (c) a predetermined time period has elapsed (e.g., 10 seconds). After the predetermined conditions are met, the end effector 114 can move to the next pair of electrodes in the sequence, and the neuromodulation algorithm can terminate when the load resistances of all individual pairs of electrodes are at or above a predetermined threshold (e.g., 100W). In various embodiments, RF energy can be applied at a predetermined frequency (e.g., 450-500 kHz) and is expected to initiate ionic stirring of a specific target structure while avoiding functional interference with non-target structures.

[0179] During and / or after neuromodulation therapy, the method is continued by detecting and optionally mapping the post-therapy bioelectrical properties of the target site. This can be performed in a manner similar to that described above. Post-therapy evaluation can indicate whether the target structure (e.g., an overactive parasympathetic nerve) has been properly modulated or ablated. If the target structure is not properly modulated (i.e., neural activity is still detected within the target structure and / or the neural activity has not decreased), the method can be continued by reapplying therapeutic neuromodulation to the target. If the target structure is properly ablated, the neuromodulation procedure can be completed. (Detection of anatomical structure and function)

[0180] Various embodiments of this technology may include features that measure the bioelectric, dielectric, and / or other properties of tissue at a target site to determine the presence, location, and / or activity of nerve structures and other anatomical structures, and optionally map the location of detected nerve structures and / or other anatomical structures. For example, the technology can be used to detect glandular structures, and optionally their myxoserous function and / or other functions. The technology can also be configured to detect vascular structures (e.g., arteries), and optionally their arterial function, volumetric pressure, and / or other functions. The mapping features discussed below may be incorporated into System 100 and / or any other devices disclosed herein to provide an accurate depiction of nerves at a target site.

[0181] Neurological and / or anatomical detection can occur (a) before the application of therapeutic neuromodulation energy to determine the presence or location of neural structures and 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 to determine the real-time effect of energy application on nerve fibers at the treatment site; and / or (c) after therapeutic neuromodulation to confirm the effectiveness of the treatment on target structures (e.g., nerves, glands, etc.). This allows for the identification of very specific anatomical structures (even down to the microscale or cellular level), and therefore provides highly targeted neuromodulation. This improves the effectiveness and efficiency of neuromodulation therapy. In addition, anatomical mapping reduces the incidental effects of neuromodulation therapy on non-target sites. Thus, targeted neuromodulation prevents vascular damage or rupture (i.e., preventing undesirable bleeding) and incidental damage to tissues that may be of concern during wound healing (e.g., when damaged tissue peels off the nasal wall).

[0182] In some embodiments, the systems disclosed herein can use bioelectrical measurements such as impedance, resistance, voltage, current density, and / or other parameters (e.g., temperature) to determine biostructures at a target site, particularly nerve, glandular, and vascular biostructures. Bioelectrical properties can be detected after the transmission of a stimulus (e.g., an electrical stimulus such as RF energy delivered via electrode 136, i.e., "dynamic" detection) and / or without the transmission of a stimulus (i.e., "static" detection).

[0183] Dynamic measurements include various embodiments for exciting neuronal activation and / or propagation, and / or detecting its primary or secondary effects. Such dynamic embodiments involve heightened states of neuronal activation and propagation and use the dynamic measurements for identifying neuronal location and function relative to adjacent tissue types. For example, a method of dynamic detection may include (1) delivering stimulating energy to a treatment site via a therapeutic device (e.g., end effector 114) to excite 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 (e.g., electrode 136) of the therapeutic device; (4) identifying the relative presence and location 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.

[0184] Static measurements include various embodiments that relate to the specific intrinsic properties of stratification or cellular composition of the treatment site or its vicinity. Static embodiments relate to the intrinsic biological and electrical properties of tissue types in or near the treatment site, stratification or cellular composition of the treatment site or its vicinity, and comparing both of the aforementioned measurements with tissue types adjacent to the treatment site (not targeted for neuromodulation). This information can be used to locate 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 reference physiological parameters using a measurement / sensing array (e.g., electrode 136) of a treatment device before ablation; (2) geometrically identifying unique tissue properties within the 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 intraprocedural physiological parameters via the measurement / sensing array during the delivery of ablation energy; and (5) determining one or more postprocedural physiological parameters via the measurement / sensing array after the delivery of ablation energy to determine the effectiveness of the delivery of ablation energy in blocking the nerves that received the ablation energy.

[0185] Following initial static and / or dynamic detection of bioelectric properties, the location of anatomical features can be used to determine where the treatment site should be located relative to various anatomical structures for therapeutically effective neuromodulation of the target parasympathetic nasal nerve. The bioelectric and other physiological properties described herein can be detected via electrodes (e.g., electrode 136 of end-effector 114), and electrode pairings on the device (e.g., end-effector 114) can be selected to acquire bioelectric data in specific zones or regions and at specific depths of the target region. Specific properties detected at or surrounding the target neuromodulation site, and associated methods for acquiring these properties, 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 providing anatomical identification, anatomical mapping, and / or neuromodulation therapy. (Neurological identification and mapping)

[0186] In many neuromodulation procedures, it is beneficial to identify the portion of the nerve that falls within the zone and / or region of influence of the energy delivered by the neuromodulation device 102 (referred to as the “zone of interest”), as well as the relative three-dimensional position of the nerve structure with respect to the neuromodulation device 102. Characterizing the portion of the nerve structure within the zone of interest, and / or determining the relative position of the nerve structure within the zone of interest, allows clinicians to (1) selectively activate a target nerve structure compared to a non-target structure (e.g., blood vessels), and (2) selectively select a specific target nerve structure (e.g., parasympathetic nerves) compared to a non-target nerve structure (e.g., sensory nerves, subgroups of nerve structures, nerve structures with a certain composition or morphology). Target structures (e.g., parasympathetic nerves) and non-target structures (e.g., blood vessels, sensory nerves, etc.) can be identified based on the unique signature of the specific structure, defined by the unique morphological composition of the structure and the bioelectrical properties associated with these morphological compositions. For example, a unique discrete frequency can be associated with the morphological composition and therefore used to identify a particular structure. Target and non-target structures can also be identified based on their relative bioelectrical activation, so as to partially select specific neural structures. Furthermore, target and non-target structures can be identified by the different detected responses of the structures to a combined injected stimulus. For example, the system described herein can detect the magnitude of the structural response and the differences in the responses of anatomical structures to different stimuli (e.g., stimuli injected at different frequencies).

[0187] For the purposes of this disclosure at least, nerves may include the following parts, defined based on their individual orientation to the zone of interest: terminal nerve structures (e.g., terminal axonal structures), branching nerve structures (e.g., branching axonal structures), and progressive nerve structures (e.g., progressive axonal structures). For example, terminal nerve structures enter the zone but do not exit it. Thus, terminal nerve structures are endpoints for nerve signaling and activation. Branching nerve structures are nerves that enter the zone of interest and increase the number of nerves exiting the zone of interest. Branching nerve structures are typically associated with a reduction in the relative geometric shape of the nerve bundle. Progressive nerve structures are nerves that enter and exit the zone of interest with substantially no change in geometric shape or numerical value.

[0188] System 100 can be used to detect voltage, current, complex impedance, resistance, dielectric constant, and / or conductivity associated with the complex action potential of a nerve, and to determine and / or map the relative position and proportion of the nerve within the zone of interest. Nerve cross-sectional area ("CSA") is expected to be due to an 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. The complex action response from larger nerves outperforms that of smaller nerves in both static and dynamic assessments. This is because, at least in part, the complex action potential is the cumulative action response from each of the axons. When using static analysis, for example, System 100 can directly measure and map the impedance or resistance of a nerve and, based on the determined impedance or resistance, determine the location and / or relative size of the nerve. In dynamic analysis, System 100 can be used to apply a stimulus to the zone of interest and detect the dynamic response of the nerve structure to the stimulus. Using this information, system 100 can determine and / or map the impedance or resistance within the zone of interest and provide information related to nerve location or relative nerve size. Nerve impedance mapping can be illustrated by showing the complex impedance that varies at specific locations at different cross-sectional depths. In other embodiments, nerve impedance or resistance can be mapped within a three-dimensional display.

[0189] Identifying the portion and / or relative position of nerves within the zone of interest can signal and / or guide the selection of one or more therapeutic parameters (e.g., electrode ablation pattern, electrode activation plan, etc.) of System 100 to improve therapeutic efficiency and effectiveness. For example, during nerve monitoring and mapping, System 100 can at least partially identify nerve directivity based on the length of nerve structures extending along the zone of interest, the relative size of nerve structures, and / or the direction of action potentials. This information can then be used by System 100 or a clinician to automatically or manually adjust therapeutic parameters (e.g., selective electrode activation, bipolar and / or multipolar activation, and / or electrode positioning) to target specific nerves or regions of nerves. For example, 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 / position mapping and / or nerve proportional mapping. In some embodiments, the structure and / or properties of the electrode 136 itself (e.g., material, surface roughening, coating, cross-sectional area, periphery, penetration, penetration depth, surface mounting, etc.) may be selected based on nerve portion and proportional mapping.

[0190] In various embodiments, therapeutic parameters and / or energy delivery parameters can be adjusted to target on-axial or near-axial progressive nerve structures and / or to avoid activating progressive nerve structures that are at least substantially perpendicular to the end-effector 114. Most on-axial or near-axial progressive nerve structures are more susceptible to the neuromodulation energy provided by the end-effector 114 than vertically progressive nerve structures, which are exposed and can only be exposed to therapeutic energy in discrete sections. Therefore, the end-effector 114 is more likely to have a further impact on on-axial or near-axial progressive nerve structures. Identification of nerve structure location (e.g., via complex impedance or resistance mapping) can also enable targeted energy delivery to progressive nerve structures rather than branching nerve structures (typically downstream of progressive nerve structures), as progressive nerve structures are closer to their nerve origin and therefore further nerves are affected by therapeutic neuromodulation, thereby resulting in more efficient treatment and / or higher efficacy of the treatment. Similarly, identification of nerve structure location can be used to target progressive and branching nerve structures compared to terminal nerve structures. In some embodiments, therapeutic parameters can be adjusted based on the detected nerve location to provide a selective regional effect. For example, a clinician may target a downstream portion of a nerve structure only if they wish to influence a partial effect on a very specific anatomical structure or location.

[0191] In various embodiments, nerve location and / or relative position of nerves can be determined by detecting nerve firing voltage and / or current over time. An array of electrodes 136 can be positioned in contact with tissue in the zone of interest, and electrodes 136 can measure voltage and / or current associated with nerve firing. This information can optionally be mapped (e.g., on a display 112) to identify the location of nerves in an overactive state (i.e., excessive parasympathetic tension). Rhinitis is at least partially a result of overfiring nerves, as this overactive state promotes excessive mucosal production and secretion. Therefore, detection of nerve firing rates via voltage and current measurements can be used to identify portions of the region of interest that include hyperparasympathetic function (i.e., nerves in a pathological state). This allows clinicians to identify specific nerves (i.e., nerves with excessive parasympathetic tension) before neuromodulation therapy, rather than simply targeting all parasympathetic nerves (including parasympathetic nerves in a non-pathological state), ensuring that the correct tissue is treated during neuromodulation therapy. Furthermore, neuronal firing rates can be detected during or after neuromodulatory therapy so that clinicians can monitor changes in neuronal firing rates and justify the effectiveness of the treatment. For example, recording a decrease or elimination of neuronal firing rates after neuromodulatory therapy can indicate that the therapy was effective in therapeutically treating excess / pathological nerves.

[0192] In various embodiments, the system 100 can detect neuronal activity using dynamic activation by injecting a stimulating signal (i.e., a signal that temporarily activates a nerve) through one or more of the electrodes 136 to induce an action potential, while the other pair of electrodes 136 can detect the bioelectrical properties of the neuronal response. The step of detecting neuronal structure using dynamic activation involves the step of detecting the location of the action potential within the zone of interest by measuring the release rate of neurons and associated processes. The ability to numerically measure, profile, map, and / or image rapid neuronal depolarization to generate accurate activity indices is a factor in measuring the release rate of neurons and their processes. An action potential causes a rapid increase in voltage across a nerve fiber, and the electrical impulse then spreads along the fiber. As an action potential occurs, the conductivity of the nerve cell membrane changes, becoming about 40 times greater than when the cell is at rest. During an action potential or neuronal depolarization, membrane resistance decreases by about 80 times, thereby also allowing the applied current to enter the intracellular space. Because intracellular space will provide additional conductive ions across a population of neurons, this leads to a net decrease in resistance during consistent neuronal activity, such as chronic parasympathetic responses. The magnitude of such rapid changes is estimated to be 2.8–3.7% with respect to peripheral nerve bundles (e.g., nerves in the nasal cavity), with local resistance changes using recordings near DCs.

[0193] The step of detecting neural structures using dynamic activation includes detecting the location of action potentials within a zone of interest by measuring the release rate of neurons and associated processes. The criterion for each release is an action potential, during which there is a depolarization of the neuronal membrane of up to 110 mV or more, lasting approximately 2 milliseconds and resulting from the transport of micromolar quantities of ions (e.g., sodium and potassium) across the cell membrane. The complex impedance or resistance change resulting from the neuronal membrane corresponds to 1,000–25 Wah. Subsequent measurement of stimulus introduction and neuronal response can attenuate noise, improve the signal-to-noise ratio, and precisely focus on the response region, thereby improving neuronal detection, measurement, and mapping.

[0194] In some embodiments, differences in the measurement of physiological parameters over time (e.g., complex impedance, resistance, voltage), which can reduce errors, can be used to generate neural profiles, spectra, or maps. For example, the sensitivity of system 100 can be improved so that the process provides repeated averaging to the stimulus. As a result, the mapping function output may be a unitless ratio between reference data and test-matched data at a single frequency and / or multiple frequencies and / or multiple amplitudes. Additional considerations may include multiple frequency assessment methods that, as a result, extend parameter assessments such as resistivity, admittivity, center frequency, or the ratio of extracellular-intracellular resistivity.

[0195] In some embodiments, system 100 may also be configured to indirectly measure the electrical activity of neural structures and quantify metabolic recovery processes that accompany action potential activity and act to restore the ion gradient to normal. These relate to the accumulation of ions in the extracellular space. Indirect measurement of electrical activity can be approximately 1,000 times larger (in millimolar units) and is therefore easier to measure, which can improve the accuracy of the measured electrical properties used to generate neural maps.

[0196] System 100 can perform dynamic nerve detection by detecting nerve firing voltage and / or current over time, and optionally, nerve firing rate, in response to external stimulation of nerves. For example, an array of electrodes 136 can be positioned in contact with tissue in a zone of interest, one or more of the electrodes 136 can be activated to inject signals into the tissue to stimulate a nerve, and other electrodes 136 in the electrode array can measure nerve voltage and / or current resulting from nerve firing in response to the stimulation. This information can optionally be mapped (e.g., on a display 112) to identify the location of nerves and, in some embodiments, to identify parasympathetic nerves in hyperactive states (e.g., rhinitis or other pathological conditions). Dynamic detection of nerve activity (voltage, current, firing rate, etc.) can be performed prior to neuromodulation therapy to detect target nerve locations, select target sites and therapeutic parameters, and ensure that the correct tissue is treated during neuromodulation therapy. Furthermore, dynamic detection of neuronal activity can be performed during or after neuromodulation therapy to enable clinicians to monitor changes in neuronal activity and justify the effectiveness of the treatment. For example, recording a decrease or elimination of neuronal activity after neuromodulation therapy can demonstrate that the therapy was effective in therapeutically treating excessive / pathological nerves.

[0197] In some embodiments, a stimulation signal can be delivered near a target nerve via one or more through-electrodes (e.g., microneedles penetrating the tissue) associated with an end-effector 114 and / or a separate device. The stimulation signal generates an action potential that causes smooth muscle cells or other cells to contract. The location and intensity of this contraction are detected via the through-electrodes, thereby indicating the distance to the nerve and / or the nerve's location relative to the stimulation needle electrode to the clinician. In some embodiments, the stimulation electrical signal may typically have a voltage of 1–2 mA or more and a pulse width of 100–200 microseconds or more. Shorter pulses of stimulation result in better discrimination of detected contractions but may require further current. The greater the distance between the electrode and the target nerve, the more energy is required to stimulate. Detection of stimulation and contraction intensity and / or location allows for discrimination of the degree to which the electrode is close or far from the nerve and can therefore be used to spatially locate the nerve. In some embodiments, a fluctuating pulse width may be used to measure the distance to the nerve. As the needle gets closer to the nerve, the pulse duration required to elicit a response gradually decreases.

[0198] To locate nerves via muscle contraction detection, system 100 can vary the pulse width or amplitude, thereby varying the energy of the stimulus delivered to the tissue via the penetrating electrode (energy = pulse width × amplitude). By varying the stimulus energy and monitoring muscle contraction via the penetrating electrode and / or other types of sensors, 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 stimulating / penetrating electrode is farther from the nerve. As the stimulating / penetrating electrode moves closer to the nerve, the amount of energy required to induce muscle contraction will decrease. For example, an array of penetrating electrodes can be positioned within the tissue in the zone of interest, and one or more of the electrodes can be activated to apply stimuli at different energy levels until a muscle contraction is induced. The nerve is localized using an iterative process (e.g., via a mapping / evaluation / feedback algorithm 110).

[0199] In some embodiments, system 100 can measure muscle activation from nerve stimulation (e.g., via electrode 136) and determine nerve positioning for nerve mapping without using through electrodes. In this embodiment, the therapeutic device targets varicose veins and vascular supply of smooth muscle cells surrounding the submucosa, and then composite 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 stimulation artifact to the occurrence of response. The corresponding amplitude is measured from baseline to negative peak and measured in millivolts (mV). Nerve latency (mean + SD) in adults typically ranges from about 2 to 6 milliseconds, more typically from about 3.4 + 0.8 to about 4.0 + 0.5 milliseconds. In addition to group assessments using surrogate nasal passages, comparative assessments comparing outputs at each time interval (particularly before and after energy delivery) may be performed. This is expected to provide an accurate assessment of the absolute value of the performance of neural function, as muscle action / activation can be used to infer neural action / activation, and while muscle action / activation is a secondary effect or byproduct, neural function is an absolute performance measure.

[0200] In some embodiments, system 100 can record the nerve magnetic field outside the nerve and determine the nerve's internal currents without physical interference of the nerve membrane. Although not constrained by theory, the contribution of currents inside the membrane to the magnetic field is two orders of magnitude larger than that from external currents, and the contribution from currents within the membrane is substantially negligible. Electrical stimulation of nerves in conjunction with measurements of the Magnetic Combined Action Field ("CAF") can produce a continuous position of current dipoles so that the location of conduction changes can be estimated (e.g., via the least-squares method). Visual representations (e.g., via display 112) using magnetic contour maps can indicate normal or abnormal nerve characteristics (e.g., normal can be identified with a characteristic quadrupole pattern propagating along the nerve) and thus indicate nerves that are suitable targets for disease, hyperactivity, and neuromodulation.

[0201] During magnetic field detection, the array of electrodes 136 can be positioned in contact with the tissue in the zone of interest, and optionally, one or more of the electrodes 136 can be activated to inject electrical stimulation into the tissue. As nerves in the zone of interest fire (either in response to stimulation or not), the nerves generate a magnetic field (similar to, for example, current-carrying wires), and thus the changing magnetic field indicates the nerve firing rate. The changing magnetic field caused by nerve firing can induce a current that can be detected by a nearby sensor wire (e.g., sensor 314) and / or a wire associated with the nearby electrodes 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) before neuromodulation therapy to detect the location of nerves, select target nerves (nerves with excessive parasympathetic tension), and ensure that the desired nerves are treated during neuromodulation therapy. Furthermore, magnetic field information can be used during or after neuromodulatory therapy to monitor changes in nerve firing rates and justify the effectiveness of the treatment.

[0202] In other embodiments, the nerve magnetic field is measured using a Hall probe or other suitable device, which may be integrated into part of a separate device delivered to the end effector 114 and / or the zone of interest. Alternatively, instead of measuring the voltage in the second wire, the changing magnetic field can be measured in the first wire (i.e., the nerve) using a Hall probe. The current traveling through the Hall probe will be deflected within the semiconductor. This will result in a voltage difference between the upper and lower portions that can be measured. In some aspects of this embodiment, three orthogonal planes are utilized.

[0203] In some embodiments, system 100 can be used to induce an electromotive force ("EMF") within a wire (i.e., a frequency-selective circuit such as a tunable / LC circuit) that is tunable to the resonant frequency of a nerve. In this embodiment, the nerve can be considered a current-carrying wire, and the firing action potential is a changing voltage. This causes a changing current, which in turn causes a changing magnetic flux (i.e., a magnetic field perpendicular to the wire). Under Faraday's law of electromagnetic induction / Faraday's principle, the changing magnetic flux induces an EMF (including a changing voltage) within a nearby sensor wire (e.g., integrated in an end effector 114, sensor 314, and / or other structure), and the changing voltage can be measured via system 100.

[0204] In a further embodiment, the sensor wire (e.g., sensor 314) is an inductor and therefore, with more turns for an increasing effect (e.g., V2, rms = Vl, rms(N2 / N1)), provides an increased magnetic connection between the nerve (i.e., the first wire) and the sensor wire (i.e., the second wire). Due to the changing magnetic field, a voltage is induced in the sensor wire, and this voltage can be measured and used to estimate the change in current in the nerve. Certain materials can be selected to improve the efficiency of EMF detection. For example, the sensor wire may contain a soft iron core or other high permeability material for the inductor.

[0205] During induced EMF detection, the end effector 114 and / or other devices, including the sensor wire, can be positioned in contact with the tissue in the zone of interest, and optionally, one or more of the electrodes 136 can be activated to inject electrical stimulation into the tissue. As nerves in the zone of interest fire (either in response to stimulation or not), the nerves generate a magnetic field (e.g., similar to a current carrier wire) that induces an electric current within the sensor wire (e.g., sensor 314). This information can be used to determine nerve locations and / or map them (e.g., on a display 112) before neuromodulation therapy to identify nerve locations, select target nerves (nerves with excessive parasympathetic tone), and ensure that desired nerves are treated during neuromodulation therapy. EMF information can also be used during or after neuromodulation therapy so that clinicians can monitor changes in nerve firing rates and justify the effectiveness of the treatment.

[0206] In some embodiments, system 100 can detect magnetic fields and / or EMFs generated at selected frequencies corresponding to specific types of nerves. The frequency of the detected signal, and thus the associated nerve type, can be selected based on an external resonant circuit. Resonance occurs on the external circuit when the frequency of the magnetic field of a particular nerve type matches and that nerve is firing. Thus, system 100 can be used to identify a specific subgroup / type of nerves.

[0207] In some embodiments, system 100 may include a variable capacitor frequency-selective circuit for identifying location and / or mapping specific nerves (e.g., parasympathetic nerves, sensory nerves, nerve fiber types, nerve subgroups, etc.). The variable capacitor frequency-selective circuit may be defined by other features of sensor 314 and / or end effector 114. Nerves have different resonant frequencies based on their function and structure. Therefore, system 100 may include a tunable LC circuit with a variable capacitor (C) and / or variable inductor (L) that can be selectively tuned to the resonant frequency of a desired nerve type. This allows for the detection of nerve 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, a tunable EC circuit may have an inductor tuned 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 permeability of the core material (e.g., from air to the core material). A system including such a tunable EC circuit offers advanced diffusion and differentiation not only in terms of the activation of nerve signals, but also in terms of the type of nerve being activated and the frequency at which the nerve is firing. (Anatomical mapping)

[0208] In various embodiments, the system 100 is further configured to provide minimally invasive anatomical mapping by using focused energy current / voltage stimulation from a spatially localized source (e.g., electrode 136) to induce changes in tissue conductivity in a zone of interest and to detect the resulting biopotential and / or bioelectrical measurements (e.g., via electrode 136). The current density within the tissue changes in response to changes in voltage applied by electrode 136, which produce changes in current that can be measured using 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 profilometry and to predict or estimate tissue structure within the zone of interest. More specifically, each cellular construct has a unique conductivity and absorption profile that may indicate a type of tissue or structure, such as bone, soft tissue, blood vessels, nerves, nerve types, and / or certain nerve structures. For example, different frequencies attenuate differently through different types of tissue. Therefore, by detecting absorption currents within a region, system 100 can determine the cellular level, enabling highly specific target localization and mapping of underlying structures, in some cases down to the submicroscale. This highly specific target identification and mapping improves the efficacy and efficiency of neuromodulation therapy, while also improving the safety profile of system 100 and reducing incidental effects on non-target structures.

[0209] To detect electrical and dielectric tissue properties (e.g., resistance, complex impedance, conductivity, and / or dielectric constant as a function of frequency), electrodes 136 and / or another electrode array are placed on the tissue in the area of ​​interest, and an internal or external source (e.g., generator 106) applies a stimulus (current / voltage) to the tissue. The electrical properties of the tissue between the source and the receiver electrodes 136, as well as the current and / or voltage at each individual receiver electrode 136, are measured. These individual measurements are then converted into an electrical map / image / profile of the tissue and can be visualized for the user on a display 112 to identify anatomical features of interest, in one embodiment, the location of firing nerves. For example, the anatomical mapping can be provided 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 map actual anatomical structures for the clinician. This information can also be used during neuromodulation therapy to monitor the progression of the treatment to biological structures and after neuromodulation therapy to justify successful treatment. In addition, anatomical mapping provided by bioelectric and / or biopotential measurements can be used to track changes in non-target tissues (e.g., blood vessels) resulting from neuromodulation therapy and to avoid negative adverse effects. For example, clinicians can identify when the therapy begins to ligate blood vessels and / or damaged tissue, modify the therapy, and avoid bleeding, adverse tissue ablation, and / or other negative adverse effects.

[0210] Furthermore, the threshold frequency of the current used to identify a specific target can subsequently be used when applying therapeutic neuromodulation energy. For example, the neuromodulation energy can be applied at a specific threshold frequency of the current that is specific to the target nerve and distinguishable from other non-targets (e.g., blood vessels, non-target nerves, etc.). Applying ablation energy at a target-specific frequency results in an electric field that generates ion agitation within the target nerve structure, leading to an osmotic potential difference in the target nerve structure. These osmotic potential differences cause dynamic changes in nerve membrane potential (due to differences in intracellular and extracellular fluid pressure) that lead to vacuolar degeneration of the target nerve structure, ultimately to necrosis. Using highly targeted threshold neuromodulation energy to initiate degeneration allows system 100 to deliver therapeutic neuromodulation to a specific target while surrounding blood vessels and other non-target structures are functionally maintained.

[0211] In some embodiments, system 100 can be further configured to detect the bioelectrical properties of tissue by non-invasively recording resistance changes during neuronal depolarization and mapping neuronal activity with electrical impedance, resistance, bioimpedance, conductivity, dielectric constant, and / or other bioelectrical measurements. Although not constrained by theory, when a nerve depolarizes, the cell membrane resistance decreases (e.g., about 80 times) so that current will pass into the intracellular space through open ion channels. Alternatively, the current remains in the extracellular space. With respect to non-invasive resistance measurement, tissue can be stimulated by applying a current of less than 100 Hz, such as applying a constant current square wave at 1 Hz with an amplitude of less than 25% of the threshold (e.g., 10%), thereby preventing or reducing the possibility that the current will not traverse into the intracellular space, or by stimulating at 2 Hz to stimulate neuronal activity. In either case, resistance and / or complex impedance are recorded by recording voltage changes. A complex impedance or resistance map or area profile can then be generated.

[0212] For impedance / conductivity / dielectric constant detection, electrodes 136 and / or another electrode array are placed on the tissue in the area of ​​interest, an internal or external source (e.g., generator 106) applies a stimulus to the tissue, and the current and / or voltage at the individual receiver electrodes 136 are measured. The stimulus can be applied at different frequencies to isolate different types of nerves. These individual measurements can then be converted into an electrical map / image / profile of the tissue and visualized for the user on display 112 to identify anatomical features of interest. Nerve mapping can also be used during neuromodulation therapy to select specific nerves for therapy, monitor the progression of treatment to nerves and other biostructures, and validate the legitimacy of successful treatment.

[0213] In some embodiments of the neurological and / or anatomical detection methods described above, the procedure may include a step of comparing intraprocedural physiological parameters with reference physiological parameters and / or other pre-obtained intraprocedural physiological parameters (within the same energy delivery phase). Such comparisons can be used to analyze changes in state in the treated tissue. Intraprocedural 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 technique, the measured reference, intraprocedural, and postprocedural parameters include complex impedance. In some embodiments of the technique, postprocedural physiological parameters are measured after a predetermined time period to allow for the dissipation of electric field effects (ionic stirring and / or thermal thresholds) and thus facilitate accurate assessment of the treatment.

[0214] In some embodiments, the anatomical mapping methods described above can be used to differentiate the depth of soft tissue within the nasal mucosa. The depth of the mucosa on the turbinates is greater, while the depth from the turbinates is shallower; therefore, identifying tissue depth in this technique also identifies the location within the nasal mucosa and the precisely targeted area. Furthermore, by providing microscale spatial impedance mapping of epithelial tissue as described above, the unique signatures inherent to stratified layers or cell bodies can be used to identify the region of interest. For example, since different regions have larger or smaller populations of specific structures such as submucosal glands, the target region can be identified through the identification of these structures.

[0215] In some embodiments, system 100 includes additional features that can be used to detect anatomical structures and map anatomical features. For example, system 100 may include an ultrasound probe for identifying nerve structures and / or other anatomical structures. Higher frequency ultrasound provides higher resolution but less penetration depth. Therefore, the frequency can be varied to achieve appropriate depth and resolution for nerve / anatomical localization. Functional identification may rely on spatial pulse length ("SPL") (wavelength multiplied by the number of cycles in the pulse). Axial resolution (SPL / 2) may also be determined to identify nerves.

[0216] In some embodiments, system 100 can be further configured to release stimuli with selective parameters that inhibit rather than fully stimulate neuronal activity, for example, in embodiments where the intensity-duration relationship for extracellular neuronal stimulation is selected and controlled, there exists a state in which the extracellular current can hyperpolarize the cell, resulting in inhibition rather than a stimulus surge behavior (i.e., a full action potential is not achieved). Both ion channel models, namely HH and RGC, suggest that it is possible to hyperpolarize a cell using appropriately designed burst extracellular stimulation rather than prolonging the stimulation. This phenomenon can be used to inhibit rather than stimulate neuronal activity during any of the neuronal detection and / or modulation embodiments described herein.

[0217] In various embodiments, System 100 may apply anatomical mapping techniques disclosed herein to identify or detect target vascular systems and surrounding biological structures before, during, and / or after treatment.

[0218] Throughout this specification, any reference to “one embodiment” or “a particular embodiment” means that a specific feature, structure, or characteristic described in relation to an embodiment is included in at least one embodiment. Therefore, expressions of the phrase “in one embodiment” or “in a particular embodiment” in various places throughout this specification do not necessarily refer to the same embodiment. Furthermore, a specific feature, structure, or characteristic may be combined in any preferred manner in one or more embodiments.

[0219] The terms and expressions used herein are for illustrative purposes only, not limitation, and the use of such terms and expressions is not intended to exclude any equivalents of any of the features (or parts thereof) shown or described, and it should be recognized that various modifications are possible within the scope of the claims. Therefore, the claims are intended to encompass all such equivalents. (Integrated by reference)

[0220] References and citations to other documents, such as patents, patent applications, patent publications, journals, books, articles, and web content, are made throughout this disclosure. All such documents are incorporated herein by reference in their entirety for any purpose. (Equal portions)

[0221] Various modifications of the present invention and many further embodiments will be apparent to those skilled in the art from the full content of this document, including references to scientific and patent documents cited herein, in addition to those shown and described herein. The subject matter of this specification contains important information, examples, and guidance that can be adapted to the practice of the present invention in various embodiments and equivalents thereof.

Claims

1. A system for treating the condition of a patient's nasal cavity, wherein the system is A therapeutic device comprising a therapeutic element positioned at the distal portion of the shaft of the therapeutic device, the therapeutic element is A therapeutic device comprising a plurality of flexible support elements, the plurality of flexible support elements cooperating to define a deformable frame, each support element comprising a loop-shaped support containing one or more pairs of bipolar electrodes positioned along its length, the frame being convertible between a thin delivery state and an expanded state to facilitate delivery of the therapeutic element to a target site in the patient's nasal cavity, and in the expanded state, one or more of the flexible support elements being configured to position one or more associated pairs of bipolar electrodes in direct contact with the target tissue at the target site, A console unit operably associated with the aforementioned therapeutic device, wherein the console unit is configured to control its operation, and the operation is, Controlling the emission of RF energy from at least one pair of bipolar electrodes to detect one or more properties of the tissue in the target site, Controlling the delivery of multiple therapeutic applications, including the emission of RF energy from at least one pair of bipolar electrodes, in order to modify the transmission of signals through the target tissue at the target site. Including the console unit and A system that includes these features.

2. The system according to claim 1, wherein the console unit is configured to control the output of RF energy from at least one pair of bipolar electrodes to acquire one or more impedance measurements.

3. The console unit comprises a hardware processor coupled to non-transient computer-readable memory containing instructions, and the instructions are, Receiving one or more impedance measurements via the at least one pair of bipolar electrodes to assess contact between the at least one pair of bipolar electrodes and the target tissue, The present invention provides feedback information to an operator via a display, wherein the feedback information includes an indication of contact between the at least one pair of bipolar electrodes and the target tissue. The system according to claim 2, wherein the processor is capable of causing the console unit to execute the following.

4. The system according to claim 3, wherein the feedback information includes an impedance measurement indicating whether contact exists between the at least one pair of bipolar electrodes and the target tissue.

5. Prior to the delivery of a therapeutic application of RF energy, the console unit receives an initial impedance measurement via the at least one pair of bipolar electrodes to assess contact between the at least one pair of bipolar electrodes and the target tissue, according to claim 2.

6. The system according to claim 5, wherein the console unit is configured to perform a reference juxtaposition assessment prior to the delivery of a therapeutic application of RF energy, based on the processing of the initial impedance measurement.

7. The system according to claim 1, wherein during the delivery of a therapeutic application of RF energy, the console unit is configured to continuously monitor impedance through the at least one pair of bipolar electrodes to assess contact between the at least one pair of bipolar electrodes and the target tissue.

8. The system according to claim 1, wherein the console unit comprises an energy generator configured to generate RF energy delivered by the at least one pair of bipolar electrodes.

9. The system according to claim 8, wherein the console unit incorporates a user interface for controlling, monitoring, and regulating the delivery of RF energy to tissue by the therapeutic element and the therapeutic device.

10. The system according to claim 1, wherein the therapeutic element delivers RF energy according to a plurality of therapeutic parameters, the therapeutic parameters include at least a predetermined time threshold.

11. The system according to claim 10, wherein the console unit is configured to continuously monitor the treatment delivery time during the delivery of RF energy as a therapeutic application.

12. The system according to claim 11, wherein the console unit stores predetermined maximum parameters for the operation of the therapeutic device, the maximum parameters include at least the predetermined time threshold.

13. The system according to claim 12, wherein the console unit automatically controls the therapeutic application of RF energy emitted from the at least one pair of bipolar electrodes, at least partially based on elapsed time, thereby maintaining the delivery of RF energy for a given therapeutic application over a predetermined therapeutic delivery time period, and maintaining the level of RF energy at a level sufficient to cause therapeutic neuromodulation of the target tissue.

14. The system according to claim 13, wherein the console unit is configured to automatically terminate the application of RF energy as a treatment when the elapsed time reaches the predetermined time threshold.

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