DEVICES, SYSTEMS, AND METHODS FOR IDENTIFYING, MONITORING, AND / OR EVALUATING THERAPEUTIC NASIAL NEUROMODULATION - Patent application

Abstract

Disclosed herein are devices, systems, and methods for identifying, monitoring, and / or evaluating therapeutic nasal neuromodulation. A targeted neuromodulation system configured in accordance with embodiments of the present technology can include, for example, an evaluation / modulation assembly including multiple electrodes located in a distal portion of a shaft. The electrodes are configured to emit stimulation energy at frequencies to identify and locate target neural structures and detect the resulting tissue bioelectrical properties. The system can also include a console that maps the location of the target neural structures. The evaluation / modulation assembly can then apply therapeutic neuromodulation energy in a highly tailored neuromodulation pattern based on the mapped location of the target neural structures. Thus, the system provides therapeutic neuromodulation to highly specific target structures while avoiding non-target structures and reducing side effects. [Selected Figure] Figure 3A

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 62 / 421,135, filed Nov. 11, 2016, which is incorporated by reference in its entirety.

[0002] The present technology relates generally to devices, systems, and methods for mapping, monitoring, and / or evaluating anatomical structures, including neural structures, within or associated with the nasal region of a patient. In particular, various embodiments of the present technology relate to devices, systems, and methods for identifying, monitoring, and / or evaluating therapeutic nasal neuromodulation. [Background technology]

[0003] Rhinosinusitis is characterized as inflammation of the nasal mucosa and refers to a group of conditions including allergic rhinitis, nonallergic rhinitis, chronic rhinitis, chronic sinusitis, and medically resistant rhinitis. Symptoms of rhinosinusitis include nasal congestion, blockage, congestion, nasal discharge (e.g., rhinorrhea and / or postnasal drip), facial pain, facial pressure, and / or reduced or lost sense of smell. Allergic rhinitis can include additional symptoms such as sneezing, watery rhinorrhea, nasal itching, and itchy or watery eyes. Severe rhinitis can lead to coexisting asthma flare-ups, sleep disorders, and reduced daily activities. Depending on the interval and type of system, rhinosinusitis can be classified into four subtypes: acute rhinosinusitis, recurrent rhinosinusitis, chronic rhinosinusitis with nasal polyposis (i.e., soft noncancerous growths inside the nostrils or sinuses), and chronic rhinosinusitis without nasal polyposis. Acute rhinosinusitis refers to symptoms lasting less than 12 weeks, while chronic rhinosinusitis (with or without nasal polyps) refers to symptoms lasting longer than 12 weeks. Recurrent sinusitis refers to four or more episodes of acute rhinosinusitis within a 12-month period, with resolution of symptoms between each episode.

[0004] There are many environmental and biological causes of rhinosinusitis. For example, nonallergic rhinosinusitis can be caused by environmental irritants (e.g., exhaust steam, cleaning fluids, latex, perfumes, dust, etc.), medications (e.g., NSAIDs, oral contraceptives, blood pressure medications including ACE inhibitors, antidepressants, etc.), foods (e.g., alcoholic beverages, spicy foods, etc.), hormonal changes (e.g., pregnancy and menstruation), and / or a deviated nasal septum. Triggers of allergic rhinitis can include exposure to seasonal allergens (e.g., exposure to environmental allergens at the same time each year), perennial allergens that occur at any time of the year (e.g., dust mites, animal dander, mold, etc.), and / or occupational allergens (e.g., certain chemicals, grains, latex, etc.).

[0005] Treatment of rhinosinusitis may include general avoidance of rhinitis triggers, nasal irrigation with saline, and / or drug therapy. Medications prescribed for rhinosinusitis include, for example, oral H1 antihistamines, topical nasal H1 antihistamines, topical intranasal corticosteroids, systemic glucocorticoids, injectable corticosteroids, anti-leukotrienes, nasal or oral decongestants, topical anticholinergics, cromoglycates, and / or anti-immunoglobulin E therapy. However, these medications have limited efficacy (e.g., 17% or less than placebo) and undesirable side effects such as sedation, irritation, loss of taste, sore throat, dry nose, epistaxis (i.e., nosebleeds), and / or headaches. Immunotherapy, including sublingual immunotherapy ("SLIT"), has also been used to treat allergic rhinitis by desensitizing patients to specific allergens through repeated administration of allergen extracts. However, immunotherapy requires long administration periods (e.g., 3-5 years for SLIT) and can result in numerous side effects, including pain and swelling at the injection site, urticaria (i.e., rash), angioedema, asthma, and anaphylaxis.

[0006] Surgical interventions have also been employed in attempts to treat patients with severe rhinitis symptoms refractory to medication. In the 1960s through the 1980s, surgery was performed to cut parasympathetic fibers in the alar canal in an attempt to reduce parasympathetic tone within the nasal mucosa. More recent attempts at vidian nerve transection were found to be 50-88% effective in treating rhinorrhea, with other concomitant benefits including improvement in the symptoms of sneezing and nasal congestion. These symptomatic improvements were also correlated with histological mucosal changes, with reductions in interstitial edema, eosinophilic cell infiltration, mast cell levels, and histamine concentrations in the denervated mucosa. However, despite the clinical and histological effectiveness of vidian nerve transection, resecting the vidian nerve has not been widely accepted, primarily due to morbidity associated with the lack of anatomical and autonomic selectivity. For example, the site of nerve transection contains preganglionic secretomotor fibers to the lacrimal gland, and thus nerve transection often results in loss of reflex tearing, i.e., lacrimation, which in severe cases can cause vision loss. Due to such irreversible complications, this technique has not been widely accepted. Furthermore, because postganglionic pterygium opercular fibers pass through the retroorbital plexus, the location of the vidian nerve resection relative to the target end organ (i.e., the nasal mucosa) may result in reinnervation via the autonomic plexus and otic ganglion projections traveling with the accessory meningeal artery, thereby negating the clinical benefit of nerve resection.

[0007] Complications associated with vidian nerve transection are generally believed to be due to the nonspecific site of autonomic denervation. As a result, surgeons have recently shifted the site of neurectomy to the postganglionic parasympathetic branch, which may have the same physiological effect as vidian nerve resection while avoiding collateral damage to lacrimal and sympathetic nerve fibers. For example, Japanese surgeons have performed transnasal inferior turbinate submucosal resection in conjunction with resection of the posterior nasal nerve ("PNN"), a postganglionic nerve pathway located further downstream than the vidian nerve. (See Kobayashi T, Hyodo M, Nakamura K, Komobuchi H, Honda N, Resection of peripheral branches of the posterior nasal nerve compared to conventional posterior neurectomy in severe allergic rhinitis. Auris Nasus Larynx. 2012 Feb 15;39:593-596) PNN neurectomy is performed at the sphenopalatine foramen, and the PNN is believed to enter the nasal region. These nerve resections are highly complex and laborious due to the lack of good surgical markers to identify the desired posterior nasal nerve, and even if the desired nerve is located, resection of the nerve is very difficult because the nerve must be separated from the surrounding vasculature (e.g., the sphenopalatine artery). [Brief description of the drawings]

[0008] Many aspects of the present technology can be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale. Emphasis instead is placed on clearly illustrating the principles of the present technology. For ease of reference, the same reference numbers may be used throughout this disclosure to identify identical, or at least generally similar or analogous components or features.

[0009] [Figure 1] 1 is a graph illustrating nerve action potentials. [Figure 2A]1 is a graph illustrating neuronal membrane potential in relation to the opening of various ion channel gatings. [Figure 2B] FIG. 1 illustrates a graph of relative neuronal membrane permeability. [Figure 3A] FIG. 1 is a partial schematic diagram of a neuromodulation and mapping system configured in accordance with an embodiment of the present technology. [Figure 3B] FIG. 3B is an enlarged isometric view of a distal portion of a neuromodulation and mapping device of the neuromodulation and mapping system of FIG. 3A configured in accordance with an embodiment of the present technology. [Figure 4A] FIG. 13 is a three-dimensional view of a projected electrode ablation pattern of a neuromodulation device configured in accordance with an embodiment of the present technology. [Figure 4B] FIG. 13 is a three-dimensional view of a projected electrode ablation pattern of a neuromodulation device configured in accordance with an embodiment of the present technology. [Figure 4C] FIG. 13 is a three-dimensional view of a projected electrode ablation pattern of a neuromodulation device configured in accordance with an embodiment of the present technology. [Diagram 5] 1 is an illustration of a projected neuromodulation area in relation to anatomical structures within an area of ​​interest in accordance with an embodiment of the present technology. [Figure 6] 1 is an illustration of neural mapping arranged in accordance with an embodiment of the present technology; [Figure 7] 1 is a block diagram illustrating a method of anatomical mapping and therapeutic neuromodulation in accordance with an embodiment of the present technology. [Figure 8A] FIG. 13 is an enlarged isometric view of a distal portion of a neuromodulation and mapping device configured in accordance with some embodiments of the present technology. [Figure 8B] FIG. 13 is an enlarged isometric view of a distal portion of a neuromodulation and mapping device configured in accordance with some embodiments of the present technology. [Figure 9] FIG. 13 is an enlarged isometric view of a distal portion of a neuromodulation and mapping device configured in accordance with some embodiments of the present technology. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The devices, systems, and methods of the present technology are configured to (1) identify treatment locations, (2) tailor treatment to a particular patient's anatomy and / or physiology, (3) adjust ongoing treatment in real time, and / or (4) determine one or more physiological parameters before, during, and / or after therapeutic nasal neuromodulation to evaluate treatment efficacy. The targeted neuroablation provided by the systems and methods described herein is expected to enhance the efficacy of neuromodulation treatment and avoid undesirable side effects. In some embodiments, the devices, systems, and methods disclosed herein are configured to measure functional / pathophysiologically specific electrical and / or dielectric properties (i.e., bioelectrical properties or parameters) of shallow heterogeneous tissues, individual cellular components, and / or components therein on high-resolution spatial grids.

[0011] Specific details of some embodiments of the present technology are described herein with reference to Figures 1-9. While many of the embodiments are described with respect to devices, systems, and methods for mapping, evaluating, and therapeutically modulating neural structures in the nasal region for the treatment of rhinitis, other applications and other embodiments in addition to those described herein are within the scope of the present technology. For example, at least some embodiments of the present technology may be useful for neural mapping and evaluation in other anatomical sites and / or for treating other conditions (e.g., chronic sinusitis and nosebleeds). It is noted that other embodiments in addition to those disclosed herein are within the scope of the present technology. Additionally, embodiments of the present technology may have configurations, components, and / or procedures different from those shown or described herein. Furthermore, one skilled in the art will understand that embodiments of the present technology can have configurations, components, and / or procedures in addition to those shown or described herein, and that these and other embodiments may be free of some of the configurations, components, and / or procedures shown or described herein without departing from the present technology. The headings provided herein are for convenience only and are not to be construed as limitations on the disclosed subject matter.

[0012] definition As used herein, the terms "distal" and "proximal" define a location or direction relative to a clinician or a clinician's control device (e.g., the handle of a neuromodulation catheter). The terms "distal" and "distally" refer to a location along the length of the device away from or in a direction away from the clinician or the clinician's control device. The terms "proximal" and "proximally" refer to a location along the length of the device near or in a direction toward the clinician or the clinician's control device.

[0013] As used herein, a "physiological parameter" refers, at least in part, to one or more of the following: cellular composition, tissue type, anatomical landscape, bioelectrical properties or parameters, electrical and dielectric measurements, impedance, resistance, voltage, current density, current frequency, membrane potential, temperature, pressure, ion concentration, neurotransmitter concentration, action potential, muscle response to a stimulus, and any derivatives (e.g., change in any of the foregoing, rate of change in any of the foregoing, etc.), and / or combinations of those as described above and / or in detail herein. A bioelectrical property or parameter refers to any measurable quantity or quality of a material (e.g., tissue) to describe the interaction between that material and an electrical or magnetic source. For example, bioelectrical parameters can include resistance, reactance, complex impedance, capacitance, inductance, dielectric constant, conductivity, voltage, current density, current frequency, and / or derivatives thereof, among other parameters.

[0014] As used herein, "treatment parameters" refers to one or more of the following: x, y, and / or z position of the treatment device and / or electrodes relative to the treated nerve, x, y, and / or z position of the electrodes relative to each other, the shape and / or layout of the active electrode array (e.g., ring-shaped, rectangular, etc.), the shape and / or size of the electrodes themselves, the number of electrodes, the number of treatments (in the same procedure or different procedures), the timing and / or actuation sequence of energy delivery from multiple electrodes, energy delivery parameters (described below), electrode polarity, electrode grouping, and the phase angle between the voltage sources driving the electrodes.

[0015] As used herein, "energy delivery parameters" refer to the amplitude, frequency, waveform, phase angle, pulse repetition frequency, and pulse width of the applied therapeutic energy.

[0016] As used herein, a "treatment site" refers to an anatomical location at or near a neural structure, such as parasympathetic fibers, sympathetic fibers, sensory fibers, group A nerve fibers, group B nerve fibers, group C nerve fibers, and / or other neural structures that will ultimately be targeted for neuromodulation. In certain embodiments of the present technology, it will be understood that the neural structure targeted for neuromodulation must first be identified and located by the present technology. Thus, a "treatment site" refers to an anatomical location that includes or is adjacent to the neural structure to be treated (e.g., within about 5 mm to about 10 mm, within about 2 mm to about 5 mm, within about 2 mm, etc.). A treatment site can also include other anatomical structures (e.g., glands) and / or avoid certain structures (e.g., ducts).

[0017] As used herein, the term "nerve structure" refers to a structure associated with a nerve or nerve group, including, among other structures, nerve bundles, axons, dendrites, cell bodies, parasympathetic fibers, sympathetic fibers, sensory fibers, group A nerve fibers, group B nerve fibers, and / or group C nerve fibers.

[0018] Relevant Anatomy and Physiology The cell body, dendrites, and axon of a neuron are surrounded by a cell membrane. The cell membrane contains various means for sending sodium ions outward. This can increase the concentration of potassium ions within the neuron. Due to the uneven distribution of these and other ions, the neuronal cell membrane carries a negative charge on the inner surface of the cell membrane, typically up to 50-70 millivolts, or even, in certain cases, more than 70 millivolts. If the membrane is shorted briefly by a change in its ion permeability, sodium ions surge inward and potassium ions surge outward for a short time. This rapid ion movement shorts adjacent regions of the cell membrane, resulting in a cycle that propagates along the membrane. This self-propagating ionic and electrical change is known as an action potential. An example of an action potential is shown in Figure 1, and the effect of various ion channels and / or transporters that open during a compound action potential is shown in Figure 2A. Furthermore, Figure 2B illustrates the effect of a compound action potential based on the permeability of certain ion channels. As described in more detail below, the neuromodulation and mapping system described herein can be used to selectively target specific ion channels to map the subsequent action potential cascade and / or neuromodulate specific ion channels to terminate subsequent action potentials (e.g., by sending a stimulating or modulating signal having a threshold frequency associated with the target). Once the action potential has passed through the region of the membrane, equilibrium is restored so that the neuron is ready for the next action potential. During this short recovery period (known as the refractory period), the membrane does not respond to any further stimuli. Action potentials are usually carried in only one direction, away from the origin of the action potential. All action potentials after initiation are identical. Thus, the information carried by the neuron is coded by the number and frequency pattern of action potentials.

[0019] The F-wave is a phenomenon defined by the second of two voltage changes observed after an electrical stimulus is applied to a nerve, and can be used to measure nerve conduction velocity and / or other physiological parameters. For example, an electrical stimulus can be applied to the distal portion of a nerve, resulting in an impulse traveling both distally (orthotropic, i.e., toward the muscle fiber) and proximally (anterotropic, i.e., back toward the ganglion body of the motor neuron in the central nervous system (CNS)). When the orthotropic stimulus reaches the muscle fiber, it elicits an initial strong response (muscle contraction). When the antitropic stimulus reaches the motor neuron cell body, some of the motor neurons backfire, giving rise to a countercurrent orthotropic wave that travels through the nerve distally toward the muscle. This stimulus elicits a small, second compound muscle action potential that defines the F-wave.

[0020] The epithelium forms a tight monolayer with stable and sufficient transepithelial resistance. + ) ion and chloride (Cl - Active secretion or absorption of charged salts, such as cations, induces a potential difference across the epithelial surface that can be measured as a voltage. For example, biopotentials can be measured by using a high impedance voltmeter between two electrodes of a neuromodulation device, such as the neuromodulation devices described below, or a separate voltage monitoring device.

[0021] In some embodiments, the incident electromagnetic fields (e.g., detected via electrodes) involving soft and hard tissues in the nose and sinus spaces (e.g., nasal mucosa, submucosal tissue composition, periosteum, and bony plates) depend on the local geometry and dielectric properties of those systems. Due to the structure of the soft and hard tissues, there are large differences in both the specific conductivity and permittivity of the soft and hard tissues. Thus, a frequency threshold level can be identified to distinguish the "deeper" mucosal tissues above the turbinates from the "shallow" tissues away from the turbinates.

[0022] Selected Embodiments of a System for Anatomical Mapping and Therapeutic Neuromodulation FIG. 3A is a partial schematic diagram of a system 300 for detecting anatomical structures and therapeutic nasal neuromodulation, configured in accordance with an embodiment of the present technology, and FIG. 3B is an enlarged isometric view of a distal portion of the system 300, configured in accordance with an embodiment of the present technology. As shown in FIG. 3A, the system 300 includes a detection and modulation catheter or device 302 ("device 302"), a console 304, and a cable 306 extending therebetween. The device 302 includes a shaft 308 having a proximal portion 308a, a distal portion 308b, and a handle 310 at the proximal portion 308a of the shaft 308, and an evaluation / modulation assembly or element 312 at the distal portion 308b of the shaft 308. The shaft 308 is configured to position the distal portion 308b intraluminally at a treatment or target site, such as in the nasal region proximate to the postganglionic parasympathetic nerves that innervate the nasal mucosa. The target site may be the area, volume, or region in which the target nerve is located and may vary in size and shape depending on the patient's anatomy. For example, the target site may be 3-5 cm below the sphenopalatine foramen ("SPF"). 2 In other embodiments, the target site may be larger, smaller, and / or located elsewhere in the nasal cavity to target desired nerve fibers. The evaluation / modulation assembly 312 may include at least one electrode 344 configured to therapeutically modulate postganglionic parasympathetic nerves via electromagnetic energy (e.g., RF energy). In certain embodiments, for example, the evaluation / modulation assembly 312 may therapeutically modulate postganglionic parasympathetic nerves that branch off from the pterygopalatine ganglion and innervate the nasal region and nasal mucosa, such as the parasympathetic nerves (e.g., posterior nasal nerves) that traverse the SPF, accessory foramina, and microforamen of the palate. The electrodes 344 and / or other sensing elements of the evaluation / modulation assembly 312 may be further configured to detect one or more physiological parameters in the area of ​​interest before, during, and / or after therapeutic neuromodulation to identify the target site, target the treatment to the patient's anatomy, and / or evaluate the effectiveness of the treatment.

[0023] In various embodiments, the evaluation / modulation assembly 312 can include one or more sensing elements 314, such as one or more of the following sensors: pressure sensors, temperature sensors (e.g., thermocouples, thermistors, etc.), flow sensors (e.g., Doppler velocity sensors, ultrasonic flow meters, etc.), flow rate sensors, complex impedance sensors, dielectric sensors, chemical sensors, biosensing elements, voltmeters, electrochemical sensors, hemodynamic sensors, optical sensors, and / or other suitable sensing devices. The sensor(s) and / or electrodes 344 can be connected to one or more wires (not shown, e.g., copper wires, etc.) that extend through the shaft 308 to transmit signals to and from the electrodes 344 and / or sensor(s). In some embodiments, the electrodes 344 and / or sensor(s) can communicate wirelessly with various components of the system 300.

[0024] In some embodiments, the evaluation / modulation assembly 312 can include an energy delivery element configured to provide therapeutic neuromodulation using modalities other than RF energy, such as cryotherapy cooling, ultrasound energy (e.g., high intensity focused ultrasound ("HIFU") energy), microwave energy (e.g., via a microwave antenna), direct heating, high and / or low power laser energy, mechanical vibration, and / or light power. In further embodiments, the evaluation / modulation assembly 312 can be configured to deliver a chemical or agent to a target site to chemically ablate or embolize a target nerve. For example, the evaluation / modulation assembly 312 can include a needle applicator extending through the access portion of the shaft 308 and / or a separate introducer, and the needle applicator can be configured to inject a chemical, such as botox, alcohol, guanethidine, ethanol, phenol, a neurotoxin, or another suitable agent selected to modify, damage, or destroy a nerve, into the target site to therapeutically modulate the target nerve.

[0025] The device 302 can be operatively coupled to the console 304 via a wired connection (e.g., via a cable 306) and / or a wireless connection. The console 304 can be configured to control, monitor, supply, and / or otherwise support the operation of the device 302. The console 304 can be further configured to generate a selected shape and / or magnitude of energy for delivery to tissue or nerves at a target site via the evaluation / modulation assembly 312, and thus the console 304 may have different configurations depending on the treatment modality of the device 302. For example, if the device 302 is configured for electrode-based, thermal element-based, and / or transducer-based treatment, the console 304 includes an energy generator 316 configured to generate RF energy (e.g., monopolar, bipolar, or multipolar RF energy), pulsed electrical energy, microwave energy, light energy, ultrasound energy (e.g., intraluminally delivered ultrasound and / or HIFU), direct thermal energy, radiation (e.g., infrared, visible light, and / or gamma radiation), and / or another suitable type of energy. When the device 302 is configured for cryotherapy treatment, the console 304 can include a refrigerant reservoir (not shown) and can be configured to supply refrigerant to the device 302. Similarly, when the device 302 is configured for chemical-based treatment (e.g., drug infusion), the console 304 can include a chemical reservoir (not shown) and can be configured to supply one or more chemicals to the device 302.

[0026] In some embodiments, the device 302 can further include a channel 324 extending along at least a portion of the shaft 308 and a port 326, where the distal portion 308b of the shaft is in communication with the port 326. In certain embodiments, the channel 324 is a fluid pathway for delivering fluid to the distal portion 308b of the shaft 308 via the port 326. For example, the channel 324 can deliver saline or other fluid to rinse the intraluminal nasal passage during delivery of the evaluation / modulation assembly 312, to flush the target site prior to applying therapeutic neuromodulation to the target site, and / or to deliver fluid to the target site during energy delivery to reduce heating or cooling of tissue adjacent the electrodes 344. In other embodiments, the channel 324 allows for drug delivery to the treatment site. For example, a needle (not shown) can protrude through the port 326 to inject or otherwise deliver nerve blocks, local anesthetics, and / or other pharmacological agents to tissue at the target site. In some embodiments, the channels 324 allow for the removal or evacuation of steam and / or smoke from the treatment site.

[0027] As further shown in FIG. 3A, the system 300 can include a controller 318 communicatively coupled to the device 302. In an exemplary embodiment, the controller 318 is housed within the console 304. In other embodiments, the controller 318 can be carried by the handle 310 of the device 302, the cable 306, a separate component, and / or another portion of the system 300. The controller 318 can be configured to initiate, terminate, and / or regulate the operation of one or more components of the device 302 (e.g., the electrodes 344) directly and / or via the console 304. The controller 318 can be configured to execute automatic control algorithms and / or receive control instructions from an operator (e.g., a clinician). For example, the controller 318 and / or other components of the console 304 (e.g., memory) can include computer-readable media bearing instructions that, when executed by the controller 318, cause the evaluation / modulation assembly 312 to perform a particular function (e.g., apply energy in a particular manner, detect impedance, detect temperature, detect nerve location or anatomical structure, etc.). Memory may include one or more of a variety of hardware devices for volatile and non-volatile storage, and may include both read-only and writeable memory. For example, memory may comprise random access memory (RAM), CPU registers, read-only memory (ROM), and writeable non-volatile memory such as flash memory, hard drives, floppy disks, CDs, DVDs, magnetic storage devices, tape drives, device buffers, etc. Memory is not a propagating signal separate from the underlying hardware, and therefore memory is non-transient.

[0028] The console 304 may also be configured to provide feedback to the operator before, during, and / or after a treatment procedure via the mapping / evaluation / feedback algorithm 320. For example, the mapping / evaluation / feedback algorithm 320 may be configured to provide information related to the location of nerves at the treatment site during monitoring and modulation, the location of other anatomical structures (e.g., conduits) at the treatment site, the temperature at the treatment site, and / or the effect of therapeutic neuromodulation on nerves at the treatment site. In certain embodiments, the mapping / evaluation / feedback algorithm 320 may include features to ensure the effectiveness of treatment and / or enhance desired performance of the system 300. For example, the mapping / evaluation / feedback algorithm 320, in conjunction with the controller 318 and the evaluation / modulation assembly 312, may be configured to monitor neural activity and / or temperature at the treatment site during treatment and automatically shut off energy delivery when the neural activity and / or temperature reaches a predetermined threshold (e.g., a threshold reduction in neural activity, a threshold maximum temperature when applying RF energy, or a threshold minimum temperature when applying cryotherapy). In other embodiments, the mapping / evaluation / feedback algorithm 320, in conjunction with the controller 318, can be configured to automatically terminate treatment after a predetermined maximum time, a predetermined maximum impedance or resistance rise in the target tissue (i.e., compared to a baseline impedance measurement), a predetermined maximum impedance of the target tissue, and / or other thresholds for biomarkers related to autonomic function. This and other information related to operation of the system 300 can be communicated to an operator via a display 322 (e.g., a monitor, touch screen, user interface, etc.) on the console 304 and / or a separate display (not shown) communicatively coupled to the console 304.

[0029] In various embodiments, the Evaluation / Modulation Assembly 312 and / or other portions of the system 300 can be configured to detect various bioelectrical parameters of tissue at the target site, and this information can be used by the Mapping / Evaluation / Feedback Algorithm 320 to determine the anatomical structure of the target site (e.g., tissue type, tissue location, vasculature, bone structure, foramen, sinuses, etc.), locate neural structures, distinguish between different types of neural structures, map the anatomical and / or neural structures at the target site, and / or identify the neuromodulation pattern of the Evaluation / Modulation Assembly 312 with respect to the patient's anatomy. For example, the Evaluation / Modulation Assembly 312 can be used to detect resistance, complex electrical impedance, dielectric properties, temperature, and / or other properties indicative of the presence of nerve fibers and / or other anatomical structures within the target region. In certain embodiments, the Evaluation / Modulation Assembly 312, in conjunction with the Mapping / Evaluation / Feedback Algorithm 320, can be used to determine the resistance (i.e., load) of the tissue (rather than impedance) to more accurately identify the tissue properties. The mapping / evaluation / feedback algorithm 320 can determine the resistance of the tissue by detecting the actual power and current of the load (e.g., via the electrodes 344). In some embodiments, the system 300 provides resistance measurements with high accuracy and very high precision, such as precision measurements down to one-hundredth of an ohm (e.g., 0.01 Ω) for a range of 1-50 Ω. The high degree of resistance detection precision provided by the system 300 allows for detection of sub-microscale structures, including neural structure firing, differences between neural structures and other anatomical structures (e.g., blood vessels), and events in different types of neural structures. This information can be analyzed by the mapping / evaluation / feedback algorithm and / or controller 318 and communicated to the operator via a high-resolution spatial grid (e.g., on the display 322) and / or other types of displays to identify neural structures and other anatomical structures at the treatment site and / or indicate predicted neuromodulation regions based on ablation patterns for the mapped anatomical structures.

[0030] The device 302 provides access to target sites deep within the nasal region, such as direct entrance of parasympathetic fibers into the nasal cavity, to therapeutically modulate autonomic activity within the nasal cavity. In certain embodiments, the device 302 can position the evaluation / modulation assembly 312 below the SPF at ostial and / or microstoma access sites, as described, for example, in U.S. Patent Application No. 15 / 153,217, filed May 10, 2016, which is incorporated herein by reference in its entirety. By manipulating the proximal portion 308a of the shaft 308 from outside the nasal entrance, the clinician can advance the shaft 308 through a tortuous intraluminal pathway through the nasal cavity and remotely manipulate the distal portion 308b of the shaft 308 via the handle 310 to position the evaluation / modulation assembly 312 at the target site. In certain embodiments, the shaft 308 can be a steerable device (e.g., a steerable catheter) with a tight bend radius (e.g., 5 mm bend radius, 4 mm bend radius, 3 mm bend radius or less) that allows the clinician to navigate through the tortuous nasal anatomy. The steerable shaft can be further configured to articulate in at least two different directions. For example, the steerable shaft 308 can include dual pull wire rings that allow the clinician to form the distal portion 308b of the shaft 308 into an "S" shape to accommodate the anatomy of the nasal region. In other embodiments, the articulating shaft 308 can be made from a substantially rigid material (e.g., a metallic material) and can include a rigid link at the distal portion 308b of the shaft 308 that resists flexing but allows for a tight bend radius (e.g., 5 mm bend radius, 4 mm bend radius, 3 mm bend radius or less). In further embodiments, the steerable shaft 308 can be a laser cut tube made from metal and / or other suitable materials. The laser cutting tube can include one or more pull wires that are manipulated by the clinician to deflect the distal portion 308b of the shaft 308, allowing the clinician to navigate the tortuous nasal anatomy to the target site.

[0031] In various embodiments, the distal portion 308b of the shaft 308 is guided into position at the target site via a guidewire (not shown) using over-the-wire (OTW) or rapid exchange (RX) techniques. For example, the distal end of the evaluation / modulation assembly 312 can include a channel for engaging with the guidewire. Intraluminal delivery of the evaluation / modulation assembly 312 can include inserting the guidewire into an orifice in communication with the nasal cavity (e.g., nasal passage or mouth) and moving the shaft 308 and / or evaluation / modulation assembly 312 along the guidewire until the evaluation / modulation assembly 312 reaches the target site (e.g., below the SPF). In further embodiments, the device 302 can be configured for delivery through a guide catheter or introducer sheath (not shown), with or without a guidewire. Image guidance (e.g., via endoscopy, computed tomography (CT), fluoroscopy, ultrasound, optical coherence tomography (OCT), and / or combinations thereof) may be used to assist the clinician in positioning and manipulating the distal portion 308b of the shaft 308 and the evaluation / modulation assembly 312.

[0032] During delivery to the target site, the evaluation / modulation assembly 312 can be prepared in a low-profile delivery state, and upon reaching the target site, the evaluation / modulation assembly 312 can be transformed to an expanded state (shown in FIGS. 3A and 3B) via manipulation of the handle 310 such that the evaluation / modulation assembly 312 contacts tissue at the target site for physiological parameter detection and / or neuromodulation. As shown in the close-up view of the evaluation / modulation assembly 312 in FIG. 3B, the evaluation / modulation assembly 312 can include a number of struts 340 spaced apart from one another to form a frame or basket 342 when the evaluation / modulation assembly 312 is in the expanded state. The struts 340 can support one or more electrodes 344 and / or other energy delivery elements. In the expanded state, the struts 340 can position at least two of the electrodes 344 toward tissue at the target site or area of ​​interest in the nasal region (e.g., proximate the palate bone below the SPF). The electrodes 344 can apply bipolar or multipolar radio frequency (RF) energy to the target site to detect bioelectrical properties of the treatment site and / or therapeutically modulate postganglionic parasympathetic nerves innervating the nasal mucosa proximate to the target site. In various embodiments, the electrodes 344 can be configured to apply pulsed RF energy at a desired duty cycle (e.g., 1.00 seconds on / 0.50 seconds off), varying power levels, and / or varying pulse durations and frequencies to regulate temperature rise in the target tissue. As shown in FIG. 3B, the distal end portion of the basket includes a double bend to enhance or maximize the contact surface area of ​​the struts 340 against the adjacent tissue (e.g., the mucosal wall).

[0033] In the embodiment shown in FIG. 3B, the basket 342 includes eight branches 346 spaced radially from one another to form an at least generally spherical structure, and each of the branches 346 includes two struts 340 positioned adjacent one another. However, in other embodiments, the basket 342 can include fewer than eight branches 346 (e.g., 2, 3, 4, 5, 6, or 7 branches), or more than eight branches 346. In further embodiments, each branch 346 of the basket 342 can include a single strut 340, more than two struts 340, and / or the number of struts 340 per branch 346 can vary. In still further embodiments, the branches 346 and struts 340 can form a basket or frame having other suitable shapes for placing the electrodes 344 in contact with tissue at the target site. For example, when in the expanded state, the struts 340 can form an oval, a hemispherical, a cylindrical structure, a pyramidal structure, and / or other suitable shapes. The structural shape of the basket 342 can also be segmented, replicated, and / or miniaturized duplications of one or more suitable shapes.

[0034] As shown in FIG. 3B, the evaluation / modulation assembly 312 can further include an internal or inner support member 348 extending distally from the distal portion 308b of the shaft 308. The distal end 350 of the support member 348 can support the distal end of the strut 340 to form a desired basket shape. For example, as shown in FIG. 3, the strut 340 can extend distally from the distal portion 308b of the shaft 308, and the distal end of the strut 340 can be attached to the distal end 350 of the support member 348. In certain embodiments, the support member 348 can include an internal channel (not shown) through which a flexible electrical connector (e.g., wire) coupled to the electrode 344 and / or other electrical features of the evaluation / modulation assembly 312 can pass. In various embodiments, the internal support member 348 can also support an electrode (not shown) at the distal end 350 and / or along the length of the support member 348.

[0035] The individual struts 340 can be made from a resilient material, such as a shape memory material (e.g., Nitinol), that allows the struts 340 to self-expand into the desired shape of the basket 342 when in an expanded state. The struts 340 can also be made from a composite wire structure having a core material with enhanced electrical conductivity and resistivity performance to enhance the signal detected by the electrodes 344. In other embodiments, the struts 340 can be made from other suitable materials and / or the evaluation / modulation assembly 312 can be mechanically expanded via a balloon or by proximal movement of the support member 348. The basket 342 and associated struts 340 can have sufficient rigidity to support the electrodes 344 and position or urge the electrodes 344 towards tissue at the target site. Additionally, the expanded basket 342 can be pressed against surrounding anatomical structures proximate the target site (e.g., nasal turbinates, palate, etc.), and the individual struts 340 can at least partially conform to the shape of the adjacent anatomical structures to secure the therapeutic element 312 at the treatment site during energy delivery. This expansion and conformability of the struts 340 can facilitate positioning the electrodes 344 in contact with the surrounding tissue at the target site.

[0036] Each strut 340 can include one or more electrodes 344 (e.g., two electrodes 344, three electrodes 344, four electrodes 344, five electrodes 344, more than five electrodes 344) and / or the number of electrodes 344 on different struts 340 can vary. In some embodiments, for example, each strut 340 can include five electrodes 344 such that each branch 346 includes ten electrodes 344 that can define five adjacent electrode pairs, but the electrodes 344 may be independently actuated and may be paired with different electrodes 344 on the branches 346 and / or other branches 346. For example, the electrodes 344 can have a length of 0.25-2.25 mm (e.g., 0.75 mm), spacing along each strut 340 of about 0.5-3.5 mm (e.g., 1.5 mm), and inter-pair spacing of about 1.5-4.0 mm (e.g., 2 mm). In other embodiments, the size and spacing of the electrodes may be different. In some embodiments, it may be beneficial to have electrodes positioned or spaced differently along the struts 340 than shown in FIG. 3B and / or asymmetrically positioned on one or more of the struts 340. For example, a central portion of the struts 340 may include a higher density of electrodes 344 than a proximal or distal portion of the struts 340. Such an asymmetric distribution of electrodes 344 may be particularly advantageous for mapping functions. This may be achieved through positioning the electrode array in a known spatial configuration and mapping electroanatomical properties at multiple planes and / or multiple or different depths in the composition of multiple (high density) actuation sequence mappings that incorporate changes in impedance of different tissue types, including different cells or functional constructs, and at different waveform frequencies (as described in more detail below).

[0037] In certain embodiments, each electrode 344 can operate independently of the other electrodes 344. For example, each electrode can be individually activated, and the polarity and amplitude of each electrode can be selected by an operator or by a control algorithm executed by the controller 318 (FIG. 3A). Selective independent control of the electrodes 344 allows the evaluation / modulation assembly 312 to detect information and deliver RF energy to highly customized regions. For example, select portions of the electrodes 344 can be activated to target specific nerve fibers in specific regions, while other electrodes 344 remain deactivated. In certain embodiments, for example, electrodes 344 may be activated over portions of the basket 342 adjacent tissue at the target site, and electrodes 344 not proximate the target tissue can remain deactivated to avoid applying energy to non-target tissue. Additionally, the electrodes 344 can be individually activated to stimulate or therapeutically modulate specific regions in specific patterns at different times (e.g., via multiplexing), which facilitates detection of anatomical parameters and / or regulated therapeutic neuromodulation over the area of ​​interest.

[0038] The electrodes 344 can be electrically coupled to the energy generator 316 (FIG. 3B) via wires (not shown) that extend from the electrodes 344 through the shaft 308 to the energy generator 316. When each of the electrodes 344 is independently controlled, each electrode 344 is coupled to a corresponding wire that extends through the shaft 308. This allows each electrode 344 to be independently actuated for stimulation or neuromodulation to provide precise ablation patterns and / or individually detected via the console 304 (FIG. 3A) to provide information specific to each electrode 344 for neural or anatomical detection and mapping. In other embodiments, multiple electrodes 344 can be controlled together and thus multiple electrodes 344 can be electrically coupled to the same wire that extends through the shaft 308. The energy generator 316 (FIG. 3A) and / or a component operably coupled thereto (e.g., a control module) can include custom algorithms for controlling the actuation of the electrodes 344. For example, the RF generator may deliver RF power at approximately 200-300 W to the electrodes 344 and may do so while actuating the electrodes 344 in a predetermined pattern selected based on the location of the evaluation / modulation assembly 312 relative to the treatment site and / or the identified location of the target nerve. In other embodiments, the energy generator 316 delivers power at lower levels for stimulation (e.g., less than 1 W, 1-5 W, 5-15 W, 15-50 W, 50-150 W, etc.) and / or at higher power levels. For example, the energy generator 316 may be configured to deliver stimulation energy pulses of 1-3 W via the electrodes 344 to stimulate specific targets within tissue.

[0039] As shown in FIG. 3B, the evaluation / modulation assembly 312 can further include one or more temperature sensors 352 disposed on the strut 340 and / or other portions of the evaluation / modulation assembly 312 and electrically coupled to the console 304 (FIG. 3A) via wires (not shown) extending through the shaft 308. In various embodiments, the temperature sensor 352 can be positioned proximate to the electrode 344 to detect the temperature at the interface between the tissue and the electrode 344 at the target site. In other embodiments, the temperature sensor 352 can penetrate the tissue at the target site (e.g., a penetrating thermocouple) to detect the temperature at a depth within the tissue. The temperature measurements can provide feedback to the operator or the system regarding the effect of the therapeutic neuromodulation on the tissue. For example, in certain embodiments, the operator may wish to prevent or reduce damage to the tissue at the treatment site (e.g., nasal mucosa), and thus the temperature sensor 352 can be used to determine whether the tissue temperature has reached a predetermined threshold for irreversible tissue damage. Once a threshold is reached, application of therapeutic neuromodulation energy can be discontinued to leave the tissue intact and avoid significant tissue loss during wound healing. In certain embodiments, energy delivery can be automatically terminated based on a mapping / evaluation / feedback algorithm 320 (FIG. 3A) stored in a console 304 (FIG. 3A) operably coupled to the temperature sensor 352.

[0040] In other embodiments, the evaluation / modulation assembly 312 can have a different configuration than that shown in FIG. 3B. For example, the evaluation / modulation assembly 312 can include similar structures and components as described in U.S. Patent Application No. 15 / 153,217, filed May 10, 2016, and incorporated herein in its entirety. In various embodiments, for example, the evaluation / modulation assembly 312 can include an expandable balloon having multiple electrodes disposed thereon at selected intervals to enhance sensing resolution. The balloon can be positioned within the basket 342 and / or can be a stand-alone structure. The balloon can also be configured to act as a heat sink by being configured to receive a coolant or medium to reduce heating of tissue adjacent to the electrodes 344 while preventing surface electrodes from contributing to thermal damage due to ablation.

[0041] 3A and 3B together, once the evaluation / modulation assembly 312 is positioned at the target site, therapeutic modulation may be applied to a precise localized region of tissue via the electrodes 344 and / or other features of the evaluation / modulation assembly 312 to induce one or more desired therapeutic neuromodulation effects to disrupt parasympathetic motor sensory function. The evaluation / modulation assembly 312 may selectively target postganglionic parasympathetic nerve fibers that innervate the nasal mucosa at a target or treatment site proximate to or at the entrance to the nasal region. For example, the evaluation / modulation assembly 312 may be positioned to apply therapeutic neuromodulation at least proximate to the SPF to therapeutically modulate nerves that enter the nasal region via the SPF, accessory foramina, and / or microforamina (e.g., at the palatine bone). By purposefully applying energy to the target site, therapeutic neuromodulation along all or at least a portion of the posterior nasal nerve fibers that enter the nasal region may be achieved. The therapeutic neuromodulation effect is generally at least in part a function of power, time, and contact between the energy delivery element and the adjacent tissue. For example, in certain embodiments, therapeutic neuromodulation of autonomic nerve fibers is produced by application of pulsed or constant waveform RF energy at a power of about 2-20 W (e.g., 5 W, 7 W, 10 W, etc.) for a period of about 1-20 seconds (e.g., 5-10 seconds, 8-10 seconds, 10-12 seconds, etc.).

[0042] The therapeutic neuromodulation effect may include partial or complete denervation via thermal ablation and / or non-ablative thermal change or damage (e.g., by sustained heating and / or resistive heating). The desired thermal heating effect may include increasing the temperature of the target nerve fiber above a desired threshold to achieve a non-ablative thermal change, or above a higher temperature to achieve an ablative thermal change. For example, the target temperature may be above the 45°C isotherm, where applicants have identified that parasympathetic modulation begins to occur. It is anticipated that therapeutic neuromodulation may be achieved at a 45°C isotherm, a 55°C isotherm, a temperature of 60°C, an isotherm between 45°C and 60°C, and / or a higher isotherm. Thus, the system 300 may be configured to apply therapeutic neuromodulation until the temperature of the target site reaches a threshold of 45°C, 55°C, 60°C, a value between 45°C and 60°C, or a value above 60°C. In various embodiments, delivering neuromodulation energy creates an electric field depth that causes ionic agitation to disrupt neural activity and / or tissue temperature, resulting in lesion size to change the conductivity / impedance / electrical properties of tissue types in the region of interest.

[0043] The hypothermic effect may also provide neuromodulation. For example, cryotherapy applicators can be used to cool tissue at a target site to provide therapeutically effective direct cell injury (e.g., necrosis), vascular injury (e.g., cell starvation from nutrients due to damage to supplying blood vessels), and sublethal hypothermia followed by apoptosis. Exposure to cryotherapy cooling can cause acute cell death (e.g., immediately after exposure) and / or delayed cell death (e.g., during tissue thawing and subsequent hyperperfusion). An embodiment of the present technology can include cooling a structure positioned at or near the tissue such that the tissue is effectively cooled to a depth where the targeted postganglionic parasympathetic nerves reside. For example, the cooling structure is cooled to a degree that causes therapeutically effective cryogenic retronasal neuromodulation.

[0044] In certain embodiments, the system 300 can determine the location and / or morphology of neural structures and / or other anatomical structures prior to treatment so that therapeutic neuromodulation can be applied to precise regions including the target neural structures while avoiding adverse effects on non-target structures such as blood vessels. As described in further detail below, the system 300 can detect various bioelectrical parameters within an area of ​​interest (e.g., within the nasal cavity) to determine the location and morphology of various neural structures (e.g., different types of neural structures, neurotropism, etc.) and / or other tissues (e.g., glandular structures, ducts, bone regions, etc.). In some embodiments, the system 300 is configured to measure biopotentials. To do so, one or more electrodes 344 are placed in contact with an epithelial surface in the area of ​​interest (e.g., treatment site). Electrical stimulation (e.g., constant or pulsed current at one or more frequencies) may be applied to tissue by one or more electrodes 344 at or near the treatment site, and voltage and / or current differences at various different frequencies between various pairs of electrodes 344 of the evaluation / modulation assembly 312 may be measured to generate a spectral profile or map of detected biopotentials that can be used to identify different types of tissue (e.g., conduits, neural structures, and / or other types of tissue) within the region of interest. For example, a current (i.e., direct or alternating current) may be applied to one pair of electrodes 344 adjacent to one another, and the resulting voltage and / or current between the other adjacent pair of electrodes 344 is measured. Of course, the current injection electrodes 344 and the measurement electrodes 344 need not be adjacent, and modifying the spacing between the two current injection electrodes 344 can affect the depth of the recorded signal. For example, closely spaced current injection electrodes 344 provide recorded signals associated with tissue deeper from the tissue surface than more spaced current injection electrodes 344 that provide recorded signals associated with tissue at a shallower depth. Recordings from electrode pairs with different spacing may be merged to provide additional information based on anatomical depth and localization.

[0045] Additionally, complex impedance and / or resistance measurements of tissue in the region of interest can be detected directly from the current-voltage data provided by biopotential measurements while different levels of frequency current are applied to the tissue (e.g., via the evaluation / modulation assembly 312). This information can be used to map neural and anatomical structures by use of frequency differential reconstruction. Applying stimuli at different frequencies will target different laminar layers or cell bodies or clusters. For example, at high signal frequencies (e.g., electrical injection or stimulation), the cell membranes of neural structures do not impede 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 a function of intracellular and extracellular tissue and fluids. At low signal frequencies, the membranes impede the flow of current providing different distinct features of the tissue such as cell shape or cell spacing. The stimulation frequency can be in the megahertz range, the kilohertz range (e.g., 400-500 kHz, 450-480 kHz, etc.), and / or other frequencies tailored to the characteristics of the tissue being stimulated and the device being used. The complex impedance or resistance levels detected from the area of ​​interest can be displayed to the user (e.g., via the display 322) to visualize the specific structure based on the stimulation frequency. For example, FIG. 6 is an illustration of neural impedance mapping at three different tissue regions and five different depths, with neural structures 609 identified by different colors or shading to allow the clinician to locate the appropriate neural target. Similar complex impedance mapping can be provided for different structures (e.g., conduits).

[0046] Furthermore, the unique morphology and composition of anatomical structures within the nasal region respond differently to different frequencies, and therefore specific frequencies can be selected to identify highly specific structures. For example, the morphology or composition of the target structure for anatomical mapping may depend on whether the cells of the tissue or other structure are membranous, laminar, and / or annular. In various embodiments, the applied stimulation signal can have a predetermined frequency that is tuned to a specific neural structure, such as the level of myelination and / or the morphology of myelination. For example, the second axon parasympathetic structure is less myelinated than the sympathetic or other structure, and therefore will have a more identifiable response (e.g., complex impedance, resistance, etc.) to the selected frequency than the sympathetic nerve. Thus, by applying signals of different frequencies to the target site, the targeted parasympathetic nerves can be differentiated from non-targeted sensory nerves, thus providing a highly specific target site for pre- or post-treatment neural mapping and / or post-treatment neural evaluation. In some embodiments, the neural and / or anatomical mapping includes measuring data of the region of interest at at least two different frequencies to identify specific anatomical structures, such that measurements are first made based on a response to an injected signal having a first frequency, and then again based on an injected signal having a second frequency different from the first frequency. For example, there are two frequencies at which a hypertrophied (i.e., disease state characteristic) submucosal target has a different electrical conductivity or permittivity compared to "normal" (i.e., healthy) tissue. The complex electrical conductivity may be determined based on one or more measured physiological parameters (e.g., complex impedance, resistance, dielectric measurements, dipole measurements, etc.) and / or adherence to one or more reliable known attributes or signatures. Additionally, the system 300 may also apply neuromodulation energy via the electrodes 344 at one or more predefined frequencies tuned to the target neural structures to provide highly targeted ablation of selected neural structures associated with the frequency(es).This highly targeted neuromodulation also reduces the side effects of neuromodulation therapy on non-target sites / structures (e.g., blood vessels) because targeted signals (having frequencies tuned to the targeted neural structures) do not have the same modulatory effect on non-target structures.

[0047] Thus, bioelectrical properties such as complex impedance and resistance may be used by the system 300 before, during, and / or after neuromodulation therapy to derive one or more treatment parameters. For example, impedance or resistance measurements may be used to confirm and / or detect contact between one or more electrodes 344 and adjacent tissue before, during, and / or after therapy. Impedance or resistance measurements may also be used to detect whether the electrodes 344 are properly placed relative to the target tissue type by determining whether the recorded spectrum has a shape consistent with an expected tissue type and / or whether successively collected spectra are reproducible. In some embodiments, impedance or resistance measurements may be used to identify treatment zone boundaries (e.g., specific neural structures to be destroyed), anatomical landmarks, anatomical structures to be avoided (e.g., vascular or neural structures that should not be destroyed), and other aspects of delivering energy to the tissue.

[0048] The bioelectrical information can be used to generate a spectral profile or map of different anatomical features tissue at the target site, and the anatomical mapping can be visualized in 3D or 2D images via the display 322 and / or other user interface to guide the selection of a suitable treatment site. This neural and anatomical mapping allows the system 300 to accurately detect and therapeutically modulate postganglionic parasympathetic fibers that innervate the mucosa at multiple nerve entry points into the nasal cavity. Furthermore, since there are no clear anatomical markers indicating the location of SPFs, accessory foramina, and microforamina, neural mapping allows the operator to identify and therapeutically modulate nerves that would otherwise be unidentifiable without complex dissection of the mucosa. In addition, anatomical mapping also allows the clinician to identify certain structures (e.g., specific arteries) that the clinician may wish to avoid during therapeutic neuromodulation. The neural and anatomical bioelectrical properties detected by the system 300 can also be used during and after treatment to determine the real-time effects of therapeutic neuromodulation based on the treatment site. For example, the mapping / evaluation / feedback algorithm 320 can also compare detected nerve location and / or activity before and after therapeutic neuromodulation and compare the change in neural activity to a predetermined threshold to assess whether the application of therapeutic neuromodulation was effective across the treatment site.

[0049] In various embodiments, the system 300 can also be configured to map expected therapeutic modulation patterns of the electrodes 344 at specific temperatures and, in certain embodiments, take into account tissue characteristics based on anatomical mapping of the target site. For example, the system 300 can be configured to map ablation patterns for specific electrode ablation patterns at a 45° C. isotherm, a 55° C. isotherm, a 65° C. isotherm, and / or other temperatures / ranges (e.g., temperatures ranging from 45° C. to 70° C. or higher) depending on the target site and / or structure.

[0050] 4A-4C illustrate three-dimensional views of such projected ablation patterns of electrodes 344 of an evaluation / modulation assembly 312 (FIG. 3A) configured in accordance with an embodiment of the present technology. The ablation pattern mapping defines a region of influence 405 (shown by dashed lines) of each electrode 344 on the surrounding tissue. The influence region 405 may correspond to a region of tissue that will be exposed to therapeutically modulating energy based on the defined electrode activation pattern. In the illustrated embodiment, the ablation pattern mapping corresponds to a device including five activated electrodes 344 on each strut 340 (FIG. 3B), however, the ablation pattern mapping can be used to illustrate ablation patterns of any number of electrodes 344, any geometry of electrode layout, and / or any ablation activation protocol (e.g., pulsed activation, multipolar / sequential activation, etc.).

[0051] With reference to FIG. 4A, in some embodiments, the ablation pattern may be configured such that each electrode 344 has an area of ​​influence 405 that only surrounds the individual electrode 344 (i.e., a "dot" pattern). In other embodiments, the ablation pattern may be such that two or more electrodes 344 may be linked together to form sub-grouped areas of influence 405 (FIG. 4B) that define a peanut-like or linear shape between the two or more electrodes 344. In further embodiments, the ablation pattern may result in a more expansive or continuous pattern in which the area of ​​influence 405 extends along multiple electrodes 344 (e.g., along each strut 340 (FIG. 3B)). In still 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 configuration, and / or other treatment parameters. A three-dimensional view of the ablation pattern (e.g., as shown in Figures 4A-4C) can be output to the display 322 (Figure 3A) and / or other user interface, allowing the clinician to visualize the changing area of ​​influence 405 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 the appropriate ablation algorithm for the patient's particular anatomy (as determined via the system 300 of Figure 3A). In other embodiments, the three-dimensional visualization of the area of ​​influence 405 can be used to illustrate the area where the electrodes 344 detect data when measuring bioelectrical properties for anatomical mapping. In this embodiment, the three-dimensional visualization can be used to determine which electrode activation pattern should be used to determine the desired property (e.g., impedance, resistance, etc.) in the desired area. In certain embodiments, it may be better to use a dot evaluation (e.g., Figure 4A), while in other embodiments, it may be more appropriate to detect information from a linear or larger contiguous area (e.g., Figures 4B and 4C).

[0052] In some embodiments, the mapped ablation pattern is overlaid on the anatomical mapping to identify which structures (e.g., neural structures, conduits, etc.) will be therapeutically modulated or otherwise affected by the treatment. For example, FIG. 5 is an illustration of a predicted or planned neuromodulation zone 507 (shown in dashed lines) in relation to previously identified anatomical structures in a zone of interest, according to an embodiment of the present technology. For example, this illustration shows a number of neural structures 509a-b, and identifies which neural structures are expected to be therapeutically modulated based on the predicted neuromodulation zone 507. As shown in FIG. 5, the expected therapeutically modulated neural structures 509a are shaded to distinguish them from the unaffected neural structures 509b. In other embodiments, different colors and / or other indicators can be used to distinguish the expected therapeutically modulated neural structures 509a from the unaffected neural structures 509b. In further embodiments, the predicted neuromodulation zone 507 and surrounding anatomical structures (based on the anatomical mapping) can be shown in a three-dimensional view (e.g., similar to FIGS. 4A-4C) and / or can include different visualization features (e.g., color coding to identify specific anatomical structures, bioelectrical properties of the target tissue, etc.). The combined predicted ablation pattern and anatomical mapping (e.g., as shown in FIG. 5) can be output to the display 322 (FIG. 3A) and / or other user interface, allowing the clinician to select an ablation algorithm appropriate for the patient's particular anatomy.

[0053] The imaging provided by system 300 and illustrated in Figures 4A-6 allows the clinician to visualize the ablation pattern prior to treatment and tailor the ablation pattern to target specific anatomical structures while avoiding others to prevent side effects. For example, the clinician can select the treatment pattern to avoid blood vessels, thereby reducing their exposure to the therapeutic neuromodulation energy. This reduces the risk of damaging or rupturing the conduits, thus preventing immediate or potential bleeding. Additionally, the selective energy application provided by neural mapping reduces side effects of therapeutic neuromodulation, such as tissue sloughing during wound healing (e.g., 1-3 weeks after ablation), thereby reducing the aspiration risk associated with the neuromodulation procedure.

[0054] The system 300 can further be configured to apply neuromodulation energy (via the electrodes 344) at a specific frequency tuned to the target neural structure, thus specifically targeting the desired neural structure over non-target structures. For example, the specific neuromodulation frequency can correspond to a frequency identified during neural mapping as corresponding to the target structure. As discussed above, the unique morphology and composition of anatomical structures respond differently to different frequencies. Thus, frequency-tuned neuromodulation energy tuned to a target structure will not have the same modulating effect on non-target structures. More specifically, applying neuromodulation energy at a target specific frequency causes ionic agitation within the target neural structure, which results in a difference in the osmotic potential of the target neural structure, and dynamic changes in neuronal membrane potential (resulting from differences in intracellular and extracellular fluid pressures). This causes degeneration, possibly resulting in 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). Thus, system 300 may use frequencies specific to neural structures to both (1) locate a target neural structure and plan an electrode ablation configuration (e.g., electrode geometry and / or activation pattern) that specifically focuses neuromodulation to the target neural structure, and (2) apply neuromodulation energy at a characteristic neural frequency to selectively ablate the neural structure in response to the characteristic neural frequency. For example, evaluation / modulation assembly 312 of system 300 may selectively stimulate and / or modulate parasympathetic fibers, sympathetic fibers, sensory fibers, alpha / beta / delta fibers, C fibers, one or more of the aforementioned anoxic terminals insulated over non-insulated fibers (areas having fibers), and / or other neural structures. In some embodiments, system 300 may also selectively target specific cells or cell regions, such as smooth muscle cells, submucosal glands, goblet cells, stratified cell regions within the nasal mucosa, during anatomical mapping and / or therapeutic modulation. Thus, system 300 provides highly selective neuromodulation therapy specific to targeted neural structures and reduces side effects of neuromodulation therapy on non-targeted structures (eg, blood vessels).

[0055] FIG. 7 is a block diagram illustrating a method 700 of anatomical mapping and therapeutic neuromodulation in accordance with an embodiment of the present technology. Although the method 700 is described below with respect to the system 300 described above with reference to FIGS. 3A-3B, the method 700 may be implemented using other suitable systems for anatomical assessment and neuromodulation therapy. As shown in FIG. 7, the method 700 includes expanding an assessment and modulation device in an area of ​​interest ("area of ​​interest"), such as a portion of the nasal cavity (block 705). For example, the assessment / modulation assembly 312 may be expanded such that at least some of the electrodes 344 are placed in contact with mucosal tissue in the area of ​​interest. The expansion device may then take bioelectrical measurements via the electrodes 344 and / or other sensors to ensure that the desired electrodes are in proper contact with tissue in the area of ​​interest (block 710). In some embodiments, for example, the system 300 detects impedance and / or resistance across the paired electrodes 344 to ensure that the desired electrodes have proper surface contact with tissue and that all electrodes 344 are functioning properly.

[0056] The method 700 continues by optionally applying electrical stimulation to the tissue (block 715) and detecting bioelectrical properties of the tissue to establish a baseline norm of the tissue (block 720). For example, the method 700 can include measuring resistance, complex impedance, current, voltage, neural firing rate, neural magnetic field, muscle activation, and / or other parameters indicative of the location and / or function of neural structures and / or other anatomical structures (e.g., glandular structures, blood vessels, etc.). In some embodiments, the electrodes 344 transmit one or more stimulation signals (e.g., pulsed or constant signals) to the area of ​​interest to stimulate neural activity and initiate action potentials (block 715). The stimulation signals can have frequencies tuned to specific target structures (e.g., specific neural structures, glandular structures, ducts, etc.) that allow for the location of the specific target structures. The specific frequency of the stimulation signal is a function of the magnetic permeability of the host, and therefore applying unique frequencies changes the attenuation of the tissue and the depth into the tissue that the RF energy will penetrate. For example, lower frequencies typically penetrate deeper into tissue than higher frequencies.

[0057] The paired non-stimulating electrodes 344 of the evaluation / modulation assembly 312 can then detect one or more bioelectrical properties of the tissue that occur in response to the stimulation, such as impedance or resistance. For example, an array of electrodes (e.g., electrodes 344) can be selectively paired together in a desired pattern (e.g., multiplexing the electrodes 344) to detect bioelectrical properties at a desired depth and / or over a desired region to provide a high level of spatial awareness in the area of ​​interest. In certain embodiments, the electrodes 344 can be paired together in a time-sequential manner according to an algorithm (e.g., provided by the mapping / evaluation / feedback algorithm 320). In various embodiments, stimulation 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 the various paired electrodes 344. For example, an anatomical or neural mapping algorithm can cause the evaluation / modulation assembly 312 to deliver pulsed RF energy at a particular frequency between different pairs of electrodes 344, and the resulting bioelectrical responses can be recorded in a time-sequential rotation until the desired area of ​​interest is properly mapped (i.e., "multiplexed"). For example, the evaluation / modulation assembly 312 can deliver stimulation energy at a first frequency through adjacent pairs of electrodes 344 for a predetermined period of time (e.g., 1-50 milliseconds), and the resulting bioelectrical activity (e.g., resistance) can be detected through one or more other pairs of electrodes 344 (e.g., spaced apart from one another to reach different depths within the tissue). The evaluation / modulation assembly 312 can then apply stimulation energy at a second frequency different from the first frequency, and the resulting bioelectrical activity can be detected through the other electrodes. This can continue if the area of ​​interest is properly mapped at the desired frequency. As described in more detail below, in some embodiments, baseline tissue bioelectrical properties (e.g., neural firing rate) are detected using static detection methods (without injection of a stimulation signal).

[0058] After detecting the baseline bioelectrical properties, the information can be used to map anatomical structures and / or functions in the area of ​​interest (block 725). For example, the bioelectrical properties detected by the electrodes 344 can be affected via the mapping / evaluation / feedback algorithm 320, and the anatomical map can be output to the user via the display 322. In some embodiments, complex impedance, dielectric, or resistance measurements can be used to map parasympathetic nerves and, optionally, identify neural structures in a hyperactive disease state. The bioelectrical properties can also be used to map other non-target structures and general anatomical structures, such as blood vessels, bones, and / or glandular structures. The anatomical locations can be provided to the user (e.g., on the display 322) as a two-dimensional map (e.g., illustrating relative intensity as shown in FIG. 6 and illustrating specific sites of potential target structures as shown in FIG. 5) and / or as a three-dimensional image. This information can be used to differentiate structures at the sub-micron cellular level and identify very specific target structures (e.g., hyperactive parasympathetic nerves). Method 700 can also predict ablation patterns of the evaluation / modulation assembly 312 based on different electrode neuromodulation protocols (e.g., as shown in FIGS. 4A-4C) and, optionally, overlay the predicted neuromodulation patterns onto the mapped anatomical structures (e.g., as shown in FIG. 5) to indicate to the user which anatomical structures will be affected by a particular neuromodulation protocol. For example, when the predicted neuromodulation patterns are displayed with respect to the mapped anatomical structures, the clinician can determine whether the target structures will be properly ablated and whether non-target structures (e.g., blood vessels) will be undesirably exposed to the therapeutic neuromodulation energy. Thus, method 700 can be used to plan a neuromodulation therapy to locate very specific target structures, avoid non-target structures, and select an electrode neuromodulation protocol.

[0059] Once the target structure is located and the desired electrode neuromodulation protocol is selected, the method 700 continues by applying therapeutic neuromodulation to the target structure (block 740). Neuromodulation energy can be applied to the tissue in a highly targeted manner that creates micro-lesions to selectively modulate the target structure while avoiding non-target vessels and leaving surrounding tissue structures healthy for effective wound healing. In some embodiments, the neuromodulation energy can be applied in a pulsed manner, whereby the tissue can be cooled between modulation pulses to ensure 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 344 in a chronological rotation until neuromodulation is predicted to be complete (i.e., "multiplexed"). For example, the evaluation / modulation assembly 312 can deliver neuromodulation energy (e.g., having a power of 5-10 W (e.g., 7 W, 8 W, 9 W) and a current of about 50-100 mA) through adjacent pairs of electrodes 344 until at least one of the following conditions is met: (a) the load resistance reaches a predetermined maximum resistance (e.g., 350 Ω), (b) the thermocouple temperature associated with the electrode pair reaches a predetermined maximum temperature (e.g., 80° C.), or (c) a predetermined period of time elapses (e.g., 10 seconds). After the predetermined condition is met, the evaluation / modulation assembly 312 can move to the next pair of electrodes in the sequence, and the neuromodulation algorithm can be terminated when all of the load resistances of the individual pair of electrodes are equal to or greater than a predetermined threshold (e.g., 300 Ω). In various embodiments, RF energy can be applied at a predetermined frequency (e.g., 450-500 kHz) and is expected to initiate ionic agitation of specific target structures while avoiding functional destruction of non-target structures.

[0060] During and / or after the neuromodulation treatment, the method continues by detecting and, optionally, mapping post-treatment bioelectrical properties of the target site (block 740). This can be performed in a manner similar to that described above with respect to blocks 715-725. A post-treatment evaluation can indicate whether the target structure (e.g., hyperactive parasympathetic nerves) has been appropriately modulated or ablated (block 745). If the target structure is not appropriately modulated (i.e., neural activity is still detected in the target structure and / or neural activity has not decreased), the method 700 can continue by applying therapeutic neuromodulation to the target again (block 735). If the target structure is appropriately ablated, the neuromodulation procedure can be completed (block 750).

[0061] Selected embodiments of anatomical structure and function detection Various embodiments of the present technology may include features that measure bioelectrical, dielectric, and / or other properties of tissue at a target site to determine the presence, location, and / or activity of neural structures and other anatomical structures, and optionally map the location of the detected neural structures and / or other anatomical structures. For example, the present technology may be used to detect glandular structures, and optionally their mucous and / or other functions. The present technology may also be configured to detect ductal structures (e.g., arteries), and optionally their arterial function, volumetric pressure, and / or other functions. The mapping features discussed below may be incorporated into any system 300 (FIGS. 3A and 3B) and / or any other device disclosed herein to provide an accurate depiction of nerves at a target site.

[0062] Nerve and / or anatomical detection can be performed (a) prior to application of therapeutic neuromodulation energy to determine the presence or location of neural and other anatomical structures (e.g., blood vessels, glands, etc.) at the target site and / or to record baseline levels 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 efficacy of treatment on the target structure (e.g., nerve glands, etc.). This allows for the identification of very specific anatomical structures (even down to the microscale or cellular level), thus providing highly targeted neuromodulation. This enhances the efficacy and efficiency of neuromodulation treatment. Furthermore, anatomical mapping reduces the side effects of neuromodulation treatment to non-target sites. Targeted neuromodulation thus inhibits damage or rupture of blood vessels (i.e., inhibits unwanted bleeding) and inhibits collateral damage to tissues that may be of concern during wound healing (e.g., when damaged tissue sloughs off the nasal wall).

[0063] In certain 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 anatomical structures at a target site, particularly nerve, gland, and vascular anatomy. Bioelectrical properties can be detected after delivery of a stimulus (e.g., an electrical stimulus such as RF energy delivered via electrodes 344 of FIGS. 3A-3B, i.e., "dynamic" detection) and / or without delivery of a stimulus (i.e., "static" detection).

[0064] Dynamic measurements include various embodiments for activating and / or detecting primary or secondary effects of neural activation and / or propagation. Such dynamic embodiments include enhanced states of neural activation and propagation and use the dynamic measurements for functional discrimination regarding nerve location and adjacent tissue type. For example, a method of dynamic detection can include (1) delivering stimulation energy to a treatment site via a treatment device (e.g., evaluation / modulation assembly 312) to activate parasympathetic nerves at the treatment site, (2) measuring one or more physiological parameters (e.g., resistance, impedance, etc.) at the treatment site via a measurement / sensing array of the treatment device (e.g., electrodes 344), (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.

[0065] Static measurements include various embodiments that relate to the specific natural properties of the layered or cellular composition at or near the treatment site. Static embodiments relate to the inherent biological and electrical properties of the tissue types at or near the treatment site, the layered or cellular compositions at or near the treatment site, and comparing both of the aforementioned measurements with tissue types adjacent to the treatment site (that are not targeted for neuromodulation). This information can be used to localize specific targets (e.g., parasympathetic fibers) and non-targets (e.g., ducts, sensory nerves, etc.). For example, a method of static detection may include: (1) determining one or more baseline physiological parameters utilizing a measurement / sensing array of the treatment device (e.g., electrode 344) prior to ablation; (2) geometrically identifying intrinsic tissue characteristics within the region of interest based on the measured physiological parameters (e.g., resistance, impedance, etc.); (3) delivering ablation energy via the treatment device to one or more nerves within the region of interest; (4) determining one or more in-procedure physiological parameters via the measurement / sensing array during delivery of the ablation energy; and (5) determining one or more post-procedure physiological parameters via the measurement / sensing array after delivery of the ablation energy to determine the effectiveness of the delivery of the ablation energy to block the nerves subjected to the ablation energy.

[0066] After initial static and / or dynamic detection of bioelectrical properties, the location of the anatomical features can be used to determine where the treatment site(s) should be with respect to various anatomical structures for therapeutically effective neuromodulation of the targeted parasympathetic nasal nerve. The bioelectrical properties and other physiological properties discussed herein can be detected via electrodes (e.g., electrodes 344 of the evaluation / modulation assembly 312 of FIGS. 3A and 3B), and electrode pairs on the device (e.g., the evaluation / modulation assembly 312) can be selected to obtain bioelectrical data in specific zones or regions and at specific depths of the target region. The specific properties detected at or near the target neuromodulation site, and associated methods for obtaining these properties, are described below. These specific detection and mapping methods discussed below are described with reference to the system 300 of FIGS. 3A and 3B, although the methods can be implemented with other suitable systems and devices that provide anatomical identification, anatomical mapping and / or neuromodulation therapy.

[0067] Neural Identification and Mapping In many neuromodulation procedures, it is beneficial to identify the portions of nerves that fall within the zone and / or region of influence of the energy delivered by the neuromodulation device 302 (FIG. 3A) (referred to as the "zone of interest"), as well as the relative three-dimensional location of the neural structures with respect to the neuromodulation device 302. By characterizing the portions of the neural structures within the zone of interest and / or determining the relative location of the neural structures within the zone of interest, the clinician can (1) selectively activate target neural structures over non-target structures (e.g., blood vessels), and (2) subselect specific target neural structures (e.g., parasympathetic nerves) over non-target neural structures (e.g., sensory nerves, subgroups of neural structures, neural structures with specific compositions or morphologies). Target structures (e.g., parasympathetic nerves) and non-target structures (e.g., blood vessels, sensory nerves, etc.) can be identified based on the unique signatures of the specific structures, defined by the unique morphological composition of the structures and the bioelectrical properties associated with these morphological compositions. For example, unique discrete frequencies can be associated with morphological compositions and thus used to identify specific structures. Target and non-target structures can also be identified based on the relative bioelectrical activation of the structures to subselect specific neuronal structures. Furthermore, target and non-target structures can be identified by the different detected responses of the structures to tailored injected stimuli. For example, the systems described herein can detect differences in the magnitude of the response of the structures and the response of the anatomical structures with respect to different stimuli (e.g., stimuli injected at different frequencies).

[0068] At least for the purposes of this disclosure, a nerve can include the following parts defined based on their respective orientations relative to the area of ​​interest: terminal nerve structures (e.g., terminal axon structures), branching nerve structures (e.g., branching axon structures), and migrating nerve structures (e.g., migrating axon structures). For example, terminal nerve structures enter the area but do not exit. Thus, terminal nerve structures are the end points of neuronal signaling and activation. Branching nerve structures are nerves that enter and increase the number of nerves that exit the area of ​​interest. Branching nerve structures are typically associated with a reduction in the relative geometry of the nerve bundle. Migrating nerve structures are nerves that enter and exit the area of ​​interest with substantially no change in geometry or value.

[0069] System 300 can be used to detect voltage, current, complex impedance, resistance, permittivity, and / or conductivity coupled to compound action potentials of nerves to determine and / or map the relative location and proportionality of nerves within an area of ​​interest. The cross-sectional area ("CSA") of neurons is expected to be due to the increase in axonal structure. Each axon is of standard size. Larger nerves (in cross-sectional dimensions) have a larger number of axons than nerves with smaller cross-sectional dimensions. In both static and dynamic assessments, the compound action response from larger nerves is larger than smaller nerves. This is at least in part because the compound action potential is a cumulative action response from each of the axons. When using static analysis, for example, system 300 can directly measure and map the impedance or resistance of the nerve and determine the location of the nerve and / or the relative size of the nerve based on the determined impedance or resistance. In dynamic analysis, system 300 can be used to apply a stimulus to an area of ​​interest and detect the dynamic response of the nerve structure to the stimulus. Using this information, the system 300 can determine and / or map impedance or resistance within an area of ​​interest to provide information regarding nerve location or relative nerve size. Neural impedance mapping can be illustrated by showing the varying complex impedance levels at specific locations at different cross-sectional depths (e.g., as shown in FIG. 6). In other embodiments, the neural impedance or resistance can be mapped to a three-dimensional display.

[0070] Identifying the portions and / or relative locations of the nerve within the area of ​​interest can inform and / or guide the selection of one or more treatment parameters (e.g., electrode ablation patterns, electrode activation plans, etc.) of the system 300 to improve treatment efficiency and effectiveness. For example, during nerve monitoring and mapping, the system 300 can identify the directionality of the nerve based at least in part on the length of the neural structures extending along the area of ​​interest, the relative sizes of the neural structures, and / or the direction of the action potentials. This information can then be used by the system 300 or a clinician to automatically or manually adjust treatment parameters (e.g., selective electrode activation, bipolar and / or multipolar activation, and / or electrode positioning) to target specific nerves or regions of the nerve. For example, the system 300 can selectively activate specific electrodes 344, combinations of electrodes (e.g., asymmetric or symmetric), and / or adjust bipolar or multipolar electrode configurations. In some embodiments, the system 300 can adjust or select waveforms, phase angles, and / or other energy delivery parameters based on the mapping of the nerve portions / locations and / or the neural proportional mapping. In some embodiments, the structure and / or properties of the electrode 344 itself (e.g., material, surface roughness, coating, cross-sectional area, perimeter, penetration, penetration depth, surface mount, etc.) may be selected based on the nerve portion and proportional mapping.

[0071] In various embodiments, the treatment parameters and / or energy delivery parameters can be adjusted to target on-axis or near-axis moving neural structures and / or to avoid activation of moving neural structures that are at least approximately perpendicular to the evaluation / modulation assembly 312. The majority of on-axis or near-axis moving neural structures are more exposed to and susceptible to the neuromodulation energy provided by the evaluation / modulation assembly 312 than vertical moving neural structures that may only be exposed to therapeutic energy at discrete cross sections. Thus, the evaluation / modulation assembly 312 is more likely to have a greater effect on on-axis or near-axis moving neural structures. Neural structure localization (e.g., via complex impedance or resistance mapping) can also allow for targeting energy delivery to moving neural structures rather than branching neural structures (typically downstream of the moving neural structures) since the moving neural structures are closer to the nerve origin, thus resulting in more nerves being affected by the therapeutic neuromodulation, thereby resulting in more efficient treatment and / or greater therapeutic effect. Similarly, neural structure localization can be used to target moving and branching neural structures rather than terminal neural structures. In some embodiments, treatment parameters can be adjusted based on the detected nerve location to provide a selective localized effect, for example, a clinician can target downstream portions of a nerve structure if they only seek to affect a localized effect on a very specific anatomical structure or location.

[0072] In various embodiments, the location of the nerves and / or the relative location of the nerves can be determined by detecting nerve firing voltage and / or current over time. An array of electrodes 344 can be positioned in contact with tissue in the area of ​​interest, and the electrodes 344 can measure voltage and / or current associated with nerve firing. This information can be optionally mapped (e.g., on the display 322) to identify the location of nerves that are in an excited state (i.e., excessive parasympathetic tone). Rhinitis is at least in part the result of excessive firing of nerves, as this excited state promotes mucus hyper-production and hypersecretion. Thus, detection of nerve firing rates via voltage and current measurements can be used to locate portions of the area of ​​interest that contain excessive parasympathetic function (i.e., diseased nerves). This allows the clinician to locate specific nerves (i.e., nerves with excessive parasympathetic tone) prior to neuromodulation treatment, rather than simply targeting all parasympathetic nerves (including non-diseased parasympathetic nerves), to ensure the correct tissue is treated during neuromodulation treatment. Furthermore, because nerve firing rate can be detected during or after neuromodulation treatment, clinicians can monitor changes in nerve firing rate to verify the efficacy of the treatment. For example, a reduction or absence of nerve firing rate following neuromodulation treatment can be recorded to indicate that the therapy is effective in therapeutically treating excited / diseased nerves.

[0073] In various embodiments, the system 300 can detect neural activity using dynamic activation by injecting a stimulation signal (i.e., a signal that temporarily activates the nerve) through one or more of the electrodes 344 to induce an action potential, and another pair of the electrodes 344 can detect bioelectrical properties of the neural response. Detecting neural structures using dynamic activation includes detecting the location of action potentials in an area of ​​interest by measuring the discharge rate and associated processes in neurons. The ability to numerically measure, profile, map, and / or image fast neuronal depolarizations to generate accurate activity indices is a factor in measuring the discharge rate in neurons and their processes. An action potential causes a sudden increase in voltage across the nerve fiber, and then the electrical impulse spreads along the fiber. When an action potential occurs, the conductance of the neuronal cell membrane changes, which is about 40 times greater than when the cell is at rest. During an action potential or depolarization of a neuron, the membrane resistance decreases by about 80 times, thereby allowing the applied current to enter the intracellular space as well. Across a population of neurons, this results in a net decrease in resistance during coherent neuronal activity such as a chronic parasympathetic response, as the intracellular space provides additional conductive ions. The magnitude of such rapid changes is estimated to be 2.8-3.7% for peripheral nerve bundles (including, for example, nerves in the nasal cavity) with local resistivity changes recorded near DC.

[0074] Detecting neural structures using dynamic activation involves detecting the location of action potentials in an area of ​​interest by measuring the discharge rate and associated processes within a neuron. The basis of each discharge is an action potential, during which time it lasts approximately 2 milliseconds and there is a depolarization of the neuronal membrane of up to 110 mV or more due to the movement of micromolar amounts of ions (e.g., sodium and potassium) across the cell membrane. The complex impedance or resistance change through the neuronal membrane drops from 1000 to 25 Ω cm. The introduction of the stimulus and subsequent measurement of the neural response is precisely focused on the responsive area, attenuating noise and improving the signal-to-noise ratio to improve neural detection, measurement, and mapping.

[0075] In some embodiments, the difference in measurements of physiological parameters (e.g., complex impedance, resistance, voltage) over time, which can reduce errors, can be used to create a neural profile, spectrum, or map. For example, the sensitivity of the system 300 can be improved because this process provides iterative averaging for stimulation. As a result, the mapping function output can be a unitless ratio between the reference and test matched data at a single frequency and / or multiple frequencies and / or multiple amplitudes. Additional considerations may include multiple frequency evaluation methods, which result in extended parameter evaluations such as resistivity, admittivity, center frequency, or ratio of extracellular to intracellular resistivity.

[0076] In some embodiments, the system 300 may also be configured to indirectly measure electrical activity of neural structures to quantify metabolic recovery processes that accompany action potential activity and act to restore ionic gradients to normal. These are associated with the accumulation of ions in the extracellular space. Indirect measurements of electrical activity can be approximately 1000 times greater (on the order of millimolar) and therefore easier to measure, which can increase the accuracy of the measured electrical properties used to generate neural maps.

[0077] The system 300 can perform dynamic neural detection by detecting nerve firing voltage and / or current, and optionally nerve firing rate, over time in response to external stimulation of the nerve. For example, an array of electrodes 344 can be positioned in contact with tissue in an area of ​​interest, one or more of the electrodes 344 can be activated to inject a signal into the tissue that stimulates the nerve, and other electrodes 344 of 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 the display 322) to identify the location of the nerve, and in certain embodiments, identify parasympathetic nerves that are in an excited state (e.g., indicative of rhinitis or other disease state). Dynamic detection of neural activity (voltage, current, firing rate, etc.) can be performed prior to neuromodulation treatment to detect target nerve location to select target sites and treatment parameters and ensure that the correct tissue is treated during neuromodulation treatment. Additionally, dynamic detection of neural activity can be performed during or after neuromodulation treatment to allow a clinician to monitor changes in neural activity to verify treatment efficacy. For example, documenting a reduction or absence of neural activity following neuromodulation therapy can indicate that the therapy is effective in therapeutically treating excited / diseased neurons.

[0078] As described in more detail below with respect to FIG. 9, in some embodiments, the stimulation signal can be delivered to the vicinity of the target nerve via one or more penetrating electrodes (e.g., microneedles that penetrate tissue) associated with the evaluation / modulation assembly 312 and / or a separate device. The stimulation signal generates an action potential, which causes smooth muscle cells or other cells to contract. The location and strength of this contraction can be detected via the penetrating electrode(s), thereby indicating to the clinician the distance to the nerve and / or the location of the nerve relative to the stimulating needle electrode. In some embodiments, the stimulation electrical signal may have a voltage of typically 1-2 mA or more, and a pulse width of typically 100-200 microseconds or more. Shorter pulses of stimulation result in better discrimination of detected contractions, but may require more current. The greater the distance between the electrode and the target nerve, the more energy is required for stimulation. Stimulation and detection of contraction strength and / or position allows for identification of how close or far the electrode is from the nerve, which can therefore be used to spatially localize the nerve. In some embodiments, various pulse widths may be used to measure the distance to the nerve. As the needle gets closer to the nerve, the pulse width needed to elicit a response becomes shorter and shorter.

[0079] To localize a nerve via muscle contraction detection, the system 300 can vary the pulse width or amplitude to vary the energy (energy = pulse width x amplitude) of the stimulation delivered to the tissue via the penetrating electrode(s). By varying the stimulation energy and monitoring muscle contraction via the penetrating electrodes and / or other types of sensors, the system 300 can estimate the distance to the nerve. If a large amount of energy is required to stimulate the nerve / contract the muscle, the stimulation / penetrating electrode is far away from the nerve. As the stimulation / penetrating electrode gets closer to the nerve, the amount of energy required to induce muscle contraction drops. For example, an array of penetrating electrodes can be placed in tissue in the area of ​​interest, and one or more electrodes can be activated to apply stimulation at different energy levels until they induce muscle contraction. An iterative process is used to localize the nerve (e.g., via the mapping / evaluation / feedback algorithm 320).

[0080] In some embodiments, the system 300 can measure muscle activation from neural stimulation (e.g., via electrodes 344) to determine neural positioning for neural mapping without the use of penetrating electrodes. In this embodiment, the treatment device targets the varicosities of smooth muscle cells surrounding the submucosal glands and vascular supply, and then targets the compound muscle action potential. This can be used to sum the voltage responses from the individual muscle fiber action potentials. The shortest latency is the time from the stimulation artifact to the onset of the response. The corresponding amplitude is measured from baseline to the negative peak and is measured in millivolts (mV). Neural latency (mean ± SD) in adults typically ranges from about 2 to 6 milliseconds, and more typically ranges from about 3.4 ± 0.8 to about 4.0 ± 0.5 milliseconds. Comparative evaluations may then be performed comparing the output at each time interval (particularly before and after energy delivery) in addition to population evaluations using alternative nasal passages. This is expected to provide an accurate assessment of the absolute value of neural function performance, since muscle action / activation may be used to infer neural activity / activation and muscle action / activation is a secondary effect or by-product, whereas neural function is an absolute performance measure.

[0081] In some embodiments, the system 300 can record the neuromagnetic field outside the nerve to determine the internal currents of the nerve without physical destruction of the nerve membrane. Without being bound by theory, the contribution to the magnetic field from the current inside the membrane is two orders of magnitude larger than that from the external currents, and the contribution from the currents within the membrane is substantially negligible. By electrically stimulating the nerve in parallel with the measurement of the magnetic compound action field ("CAF"), the continuous location of the current dipole can be obtained so that the location of the conduction changes can be estimated (e.g., by least squares methods). A visual representation (e.g., via the display 322) using a magnetic contour map can indicate normal or non-normal nerve characteristics (e.g., normal can be equated with a characteristic quadrupole pattern propagating along the nerve), and therefore which nerves are in disease, hyperactive states, and suitable targets for neuromodulation.

[0082] During magnetic field detection, an array of electrodes 344 can be positioned in contact with tissue in the area of ​​interest, and optionally, one or more of the electrodes 344 can be activated to inject electrical stimulation into the tissue. When a nerve in the area of ​​interest fires (either in response to a stimulus or in its absence), the nerve generates a magnetic field (e.g., similar to a wire carrying an electric current), and thus changes in the magnetic field are indicative of the nerve's neural firing rate. The changing magnetic field caused by the nerve firing can induce a current that is detected by a nearby sensor wire (e.g., sensor 314) and / or a wire associated with a nearby electrode 344. By measuring this current, the magnetic field strength can be determined. Prior to neuromodulation treatment, the magnetic field can be optionally mapped (e.g., on the display 322) to locate the nerve and select a target nerve (a nerve with excessive parasympathetic tone) to thereby ensure that the desired nerve is treated during neuromodulation treatment. Additionally, magnetic field information can be used during or after neuromodulation treatment, allowing the clinician to monitor changes in nerve firing rate to verify treatment efficacy.

[0083] In other embodiments, the neuromagnetic fields are measured using a Hall probe or other suitable device, which may be integrated into the evaluation / modulation assembly 312 and / or part of a separate device delivered to the area of ​​interest. Alternatively, rather than measuring the voltage of a second wire, a Hall probe may be used to measure the changing magnetic field in the original wire (i.e., the nerve). The current passing through the Hall probe is deflected in the semiconductor. This creates a voltage difference between the top and bottom, which can be measured. In some aspects of this embodiment, three orthogonal planes are utilized.

[0084] In some embodiments, system 300 can be used to induce an electromotive force ("EMF") in a wire (i.e., a frequency selective circuit such as a tunable / LC circuit) that is tunable to the resonant frequency of the nerve. In this embodiment, the nerve can be thought of as a wire carrying a current, 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 Induction / Faraday's Principle, the changing magnetic flux induces an EMF (including a changing voltage) in a nearby sensor wire (e.g., incorporated into evaluation / modulation assembly 312, sensor 314, and / or other structure), and the changing voltage can be measured via system 300.

[0085] In further embodiments, the sensor wire (e.g., sensor 314) is an inductor, thus providing an increased magnetic link between the nerve (i.e., the first wire) and the sensor wire (i.e., the second wire), and has more turns to enhance the effect. (e.g., V2,rms=V1,rms(N2 / N1)). Due to the changing magnetic field, a voltage is induced in the sensor wire, which can be measured and used to estimate the current change in the nerve. Certain materials can be selected to enhance the efficiency of EMF detection. For example, the sensor wire can include a soft iron core or other highly permeable material for the inductor.

[0086] During induced EMF detection, the evaluation / modulation assembly 312 and / or other devices including the sensor wires are positioned in contact with tissue in the area of ​​interest and can optionally activate one or more of the electrodes 344 to inject electrical stimulation into the tissue. When a nerve in the area of ​​interest fires (either in response to a stimulus or in its absence), the nerve generates a magnetic field (e.g., similar to a wire carrying a current) that induces a current in the sensor wire (e.g., sensor 314). This information can be used to determine the nerve location and / or map the nerve (e.g., on the display 322) prior to neuromodulation treatment to identify the nerve location and select a target nerve (a nerve with excessive parasympathetic tone) to ensure that the desired nerve is treated during neuromodulation treatment. The EMF information can be used during or after neuromodulation treatment so that the clinician can monitor changes in nerve firing rate to verify treatment effectiveness.

[0087] In some embodiments, the system 300 can detect magnetic fields and / or EMFs generated at selected frequencies corresponding to specific types of nerves. The frequency of the detected signal, and by extension the associated nerve type, can be selected based on an external resonant circuit. Resonance occurs in the external circuit when the external circuit matches the frequency of the magnetic field of a specific nerve type and that nerve is firing. In this manner, the system 300 can be used to locate specific subgroups / types of nerves.

[0088] In some embodiments, the system 300 can include a variable capacitor frequency selection circuit for locating and / or mapping specific nerves (e.g., parasympathetic, sensory, nerve fiber type, nerve subgroup, etc.). The variable capacitor frequency selection circuit can be defined by other features of the sensor 314 and / or the evaluation / modulation assembly 312. Nerves have different resonant frequencies based on their function and structure. Thus, the system 300 can include a tunable LC circuit having a variable capacitor (C) and / or a variable inductor (L) that can be selectively tuned to the resonant frequency of a desired nerve type. This allows for detection of neural activity associated only with the selected nerve type and its associated resonant frequency. Tuning can be achieved by moving the core in and out of the inductor. For example, the tunable LC circuit can tune the inductor by (i) changing the number of coils around the core, (ii) changing the cross-sectional area of ​​the coils around the core, (iii) changing the length of the coils, and / or (iv) changing the magnetic permeability of the core material (e.g., from air to the core material). Systems including such tunable LC circuits provide a high degree of seeding and discrimination not only with respect to neural signal activation, but also with respect to the types of neurons that are activated and the frequency at which they fire.

[0089] Anatomical Mapping In various embodiments, the system 300 is further configured to provide minimally invasive anatomical mapping using focused energy current / voltage stimulation from a spatially localized source (e.g., electrode 344) to induce changes in the electrical conductivity of tissue in an area of ​​interest and detect the resulting biopotential and / or bioelectrical measurements (e.g., via electrode 344). The current density in the tissue changes in response to changes in voltage applied by electrode 344, which produces changes in current that can be measured using the evaluation / modulation assembly 312, and / or other parts of the system 300. The results of the bioelectrical and / or biopotential measurements can be used to predict or estimate relative absorption profilometry to predict or estimate tissue structures in the area of ​​interest. More specifically, each cellular structure has a unique electrical conductivity and absorption profile that can be indicative of a type of tissue or structure, such as bone, soft tissue, conduit, nerve, type of nerve, and / or a particular nerve structure. For example, different frequencies attenuate differently through different types of tissue. Thus, by detecting the absorbed current within the region, system 300 can determine the underlying structures, in some cases down to the sub-microscale cellular level enabling highly specific target localization and mapping. This highly specific target identification and mapping enhances the efficacy and efficiency of neuromodulation therapy while also enhancing the safety profile of system 300 reducing collateral effects on non-target structures.

[0090] To detect electrical and dielectric tissue properties (e.g., resistance, complex impedance, conductivity, and / or permittivity as a function of frequency), an electrode 344 and / or another electrode array is placed on the tissue in the region of interest, and an internal or external source (e.g., generator 316) applies a stimulus (current / voltage) to the tissue. The electrical properties of the tissue between the source and receiver electrodes 344 are measured, as well as the current and / or voltage at each individual receiver electrode 344. These individual measurements can then be converted into an electrical map / image / profile of the tissue and visualized for the user on the display 322 to identify anatomical features of interest, and in certain embodiments, the location of firing nerves. For example, the anatomical mapping can be provided as a color-coded or grayscale 3- or 2-dimensional map showing different intensities of specific bioelectrical properties (e.g., resistance, impedance, etc.), or the information can be processed to map the actual anatomical structures for the clinician. This information can also be used during neuromodulation treatment to monitor the progress of the treatment with respect to the anatomical structures, and after neuromodulation treatment to verify the success of the treatment. Additionally, the anatomical mapping provided by bioelectrical and / or biopotential measurements can be used to track changes to non-target tissues (e.g., ducts) due to neuromodulation therapy to avoid negative side effects. For example, a clinician can identify when a therapy begins to ligate ducts and / or damage tissue and can modify the therapy to avoid bleeding, harmful tissue ablation, and / or other negative side effects.

[0091] Additionally, the threshold frequency of current used to identify a particular target can then be used when applying therapeutic neuromodulation energy. For example, neuromodulation energy can be applied at a particular threshold frequency of current that is specific to the target neuron and distinct 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 creates ionic agitation within the target neural structure, which leads to differences in osmotic potential of the target neural structure. These osmotic potential differences cause dynamic changes in neuronal membrane potential (resulting from differences between intracellular and extracellular fluid pressures), which results in vacuolar degeneration and ultimately necrosis of the target neural structure. By initiating degeneration using a highly targeted threshold neuromodulation energy, system 300 can deliver therapeutic neuromodulation to a specific target while surrounding blood vessels and other non-target structures remain functional.

[0092] In some embodiments, the system 300 can be further configured to detect bioelectrical properties of tissue by non-invasively recording resistance changes during neuronal depolarization to map neural activity with electrical impedance, resistance, bioimpedance, conductivity, permittivity, and / or other bioelectrical measurements. Without being bound by theory, when a nerve depolarizes, cell membrane resistance decreases (e.g., by about 80 times), so that current flows through open ion channels into the intracellular space. Otherwise, the current remains in the extracellular space. For non-invasive resistance measurements, the tissue can be stimulated by applying a current less than 100 Hz, such as applying a constant current square wave at 1 Hz with an amplitude less than 25% (e.g., 10%) of the threshold for stimulating neuronal activity, thereby preventing or reducing the possibility that the current will not cross the intracellular space or stimulate at 2 Hz. In either case, the resistance and / or complex impedance is recorded by recording the voltage changes. A complex impedance or resistance map or profile of the area (e.g., as shown in FIG. 6) can then be generated.

[0093] For impedance / conductivity / permittivity sensing, an electrode 344 and / or another electrode array is placed on the tissue in the region of interest, an internal or external source (e.g., generator 316) applies stimulation to the tissue, and the current and / or voltage at the individual receiver electrodes 344 is measured. Stimuli 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 a user on the display 322 to identify anatomical features of interest. Neuromapping can also be used during neuromodulation therapy to select specific nerves for treatment, monitor the progress of treatment with respect to nerves and other anatomical structures, and verify successful treatment.

[0094] In some embodiments of the neural and / or anatomical detection methods described above, the procedure may include comparing the intra-procedural physiological parameter(s) (within the same energy delivery phase) with the baseline physiological parameter(s) and / or other previously acquired intra-procedural physiological parameter(s). Such comparisons can be used to analyze condition changes in the treated tissue. The intra-procedural physiological parameter(s) may also be compared with one or more pre-defined thresholds, for example, to indicate when to stop delivery of therapeutic energy. In some embodiments of the present technology, the measured baseline, intra-procedural and post-procedural parameters include complex impedance. In some embodiments of the present technology, the post-procedural physiological parameters are measured after a pre-defined period to allow dissipation of electric field effects (ionic agitation and / or thermal thresholds), thus facilitating accurate evaluation of the treatment.

[0095] In some embodiments, the above-mentioned anatomical mapping method can be used to identify the depth of soft tissues in the nasal mucosa. The mucosa above the nasal turbinates has a large depth, while the depth from the nasal turbinates is shallow, so identifying the depth of tissues in this technique also identifies the location in the nasal mucosa and exactly where to target. Furthermore, by providing microscale spatial impedance mapping of epithelial tissue as described above, the unique signature of stratification or cell bodies can be used to identify the region of interest. For example, different regions have larger or smaller populations of certain structures, such as submucosal glands, so target regions can be identified through the identification of these structures.

[0096] In some embodiments, the system 300 includes additional features that can be used to detect anatomical structures and map anatomical features. For example, the system 300 can include an ultrasound probe to identify neural structures and / or other anatomical structures. Higher frequency ultrasound provides higher resolution but shallower penetration depth. Thus, the frequency can be varied to achieve appropriate depth and resolution for neural / anatomical localization. Functional discrimination may depend on the spatial pulse length ("SPL") (wavelength multiplied by the number of cycles in the pulse). Axial resolution (SPL / 2) may also be determined to locate nerves.

[0097] In some embodiments, the system 300 can be further configured to deliver stimulation with selective parameters that suppress rather than fully stimulate neural activity. For example, in embodiments in which the intensity-duration relationship for extracellular neural stimulation is selected and controlled, the extracellular current can hyperpolarize the cell, and conditions exist that result in suppression (i.e., full action potentials are not achieved) rather than stimulation spiking behavior. Both models of ion channels, HH and RGC, suggest that it is possible to hyperpolarize cells with appropriately designed burst extracellular stimulation rather than extending the stimulation. This phenomenon can be used to suppress rather than stimulate neural activity during any of the neural detection and / or modulation embodiments described herein.

[0098] SELECTED EMBODIMENTS OF THE EVALUATION AND NEUROMODULATION DEVICE 8A and 8B are isometric views of a distal portion of a neuromodulation and mapping device 802 ("device 802") configured in accordance with an embodiment of the present technology. The device 802 can include various features generally similar to those of the device 302 described above with reference to FIGS. 3A and 3B. For example, the device 802 includes an evaluation / modulation assembly 812 at a distal portion 308b of the shaft 308. The evaluation / modulation 812 includes a plurality of struts 340 forming branches 346 and defining an expandable frame or basket 342, and optionally includes one or more electrodes 344 disposed on one or more of the struts 340. As shown in FIGS. 8A and 8B, the device 802 can further include an expandable member 856 (e.g., a balloon) supported by the support member 348 and expandable within the basket 342. The expandable member 856 can include one or more electrodes 858 extending in a circumferential pattern across an outer surface of the expandable member 856. For example, one or more electrodes 858 can define a coil shape disposed on the expandable member 856. The electrodes 858 can be used for detection of bioelectrical characteristics (e.g., complex impedance, resistance, etc.) to enable mapping of anatomical structures in an area of ​​interest before, during, and / or after therapeutic neuromodulation via the other electrodes 344. In other embodiments, the electrodes 858 can be configured to apply energy for therapeutic neuromodulation.

[0099] As shown in FIG. 8B, the electrode(s) 858 may be positioned over a substantial portion of the expandable member 856, demonstrating an expanded area over which impedance and / or other properties may be detected across the tissue, thus providing more detailed mapping of the tissue and nerves at the treatment site. The expandable member 856 may also conform closely to adjacent tissue in the area of ​​interest, thus facilitating contact between the electrode(s) 858 and the tissue. In other embodiments, the electrodes 858 may have different configurations on the outer surface of the expandable member 856. When there are multiple electrodes 358, individual electrodes 858 may be selectively activated with a particular polarity, and thus the electrode array may be configured in a variety of static configurations and dynamically changing sequences (e.g., application of semi-polar currents) that may be advantageous for mapping functions.

[0100] In operation, the expandable member 856 can be inflated or otherwise expanded to place at least a portion of the electrode 858 in contact with tissue at the target site (FIG. 8B). The electrode 858 can measure various bioelectrical properties of tissue (e.g., impedance, action potential, etc.) to detect, locate and / or map neural structures and / or other anatomical structures in the area of ​​interest. In certain embodiments, the electrode 344 on the strut 340 and / or a portion of the electrode 858 on the expandable member 856 can apply a stimulation pulse of RF energy and the electrode 858 can detect the resulting neural response. After mapping, the expandable member 856 can be contracted or compressed (FIG. 8A) and the electrode 344 on the strut 340 can apply therapeutically effective neuromodulation energy to the target site. For example, the ablation pattern of the electrode 344 can be based on neural locations identified via information detected from the sensing electrode 858 on the expandable member 856. In other embodiments, the expandable member 856 may remain expanded during neuromodulation, and the electrodes 858 may detect neural activity during the neuromodulation procedure, or the electrodes 858 themselves may be configured to apply neuromodulation energy to the treatment site. After applying the neuromodulation energy, the electrodes 858 on the expandable member 856 may again be placed in contact with tissue at the target site and may be used to record bioelectrical properties (e.g., impedance, resistance, voltage, etc.). The detected properties obtained before, during, and / or after neuromodulation may be compared to one another to determine whether the neuromodulation was therapeutically effective. If not, the electrodes 344 may again apply therapeutic neuromodulation energy to the same treatment site, or the configuration of the active electrodes 344 may be changed to apply therapeutic neuromodulation energy in a different pattern or sequence, and / or the evaluation / modulation assembly 812 may be moved to a different treatment site.

[0101] FIG. 9 is an enlarged isometric view of a distal portion of a neuromodulation and mapping device 902 ("device 902") configured in accordance with some embodiments of the present technology. The device 902 can include various features generally similar to those of the device 802 described above with reference to FIGS. 8A and 8B. For example, the device 902 includes an evaluation / modulation assembly 912 including a plurality of struts 340 (optionally including electrodes 344 disposed thereon) forming an expandable frame or basket 342, and an expandable member 856 (e.g., a balloon) expandable within the basket 342 via an expansion medium (e.g., fluid, coolant, etc.). As shown in FIG. 9, the expandable member 856 includes one or more protruding or penetrating electrodes 960 that extend across an outer surface of the expandable member 856 in a circumferential pattern to define a three-dimensional microneedle array. The penetrating electrodes 960 can be very small needles and / or other structures with sharp end portions that penetrate a small depth into adjacent tissue when the expandable member 856 is expanded. For example, the needle electrodes 960 may have a micrometer-level tip diameter (e.g., 1 micrometer diameter, 2 micrometer diameter, 3 micrometer diameter, 1-20 micrometer diameter, etc.), a length of 50-350 micrometers (e.g., 150 micrometers, 210 micrometers, 250 micrometers, etc.), and / or a tip coated with platinum black and / or other suitable material. In other embodiments, the protruding needle electrodes 960 have different sizes, different material compositions, and / or are arranged in different patterns (e.g., asymmetric patterns) across the expandable member 856 that facilitate penetration into adjacent tissue and / or detection of desired tissue parameters. In some embodiments, for example, the penetrating electrodes 960 can be fabricated by selective vapor-liquid-solid growth of silicon wires. In further embodiments, the penetrating electrodes 960 can define microneedle arrays on different portions of the device 902 (e.g., along the struts 340) and / or on a substrate separate from the evaluation / modulation assembly 912.For example, the penetrating electrodes 960 can be positioned on a substrate (e.g., a paddle) that can be pressed into contact with the tissue to move the electrodes 960 a small depth into the tissue. The penetrating electrodes 960 can also be deployable and / or retractable. In some embodiments, the penetrating electrodes 960 can be integrated with metal oxide semiconductor processes for high performance on-chip electronics configurations. In some embodiments, the electrodes 344 on the posts 340 and / or other electrodes on the evaluation / modulation assembly 912 may be replaced by deployable and / or protruding / retractable penetrating needle electrodes.

[0102] The electrodes 960 can be used for detection of bioelectrical characteristics (e.g., impedance, resistance, etc.) and / or other detectable parameters to enable mapping of nerves and / or other anatomical structures in the area of ​​interest before, during, and / or after therapeutic neuromodulation via the other electrodes 344. In other embodiments, the penetrating electrodes 960 can be configured to apply energy for therapeutic neuromodulation. The device 902 is expected to provide high spatial resolution and a high level of accuracy while requiring only a minimal level of invasiveness due to the large area covered by the penetrating electrodes, the high density of electrodes 960 over that area, and the penetration into the tissue of interest. In some embodiments, for example, the output / input signal amplitude ratio may be >90% from about 40 Hz to about 10 KHz. The device 902 can be used in both chronic and acute cases.

[0103] In various embodiments, the expandable member 856 of the devices 802 and 902 described above with respect to Figures 8A-9 can be used as a drug delivery mechanism to deliver local anesthetics, neurotoxins (e.g., for stimulating or modulating nerves at a target site), and / or other drugs or chemicals pre- or post-procedure. The expandable member 856 can be made of a porous material with multiple openings or voids for drug clearance (e.g., eluting a drug disposed within the expandable member 856). The expandable member 856 can also include a drug loaded or embedded within the walls of the expandable member 856, such that pressure against the drug-loaded walls by tissue causes drug elution. The neural and anatomical mapping systems and methods described above can be used to ensure accuracy and precision of drug delivery.

[0104] Any of the therapeutic or sensing assemblies and devices disclosed herein may be semi-permanently implanted rather than connected to a catheter shaft (for temporary delivery to a treatment site). For implanted embodiments, any of the devices and methods disclosed herein may be used to locate the appropriate implant site, position the device for long-term implantation, verify device function in-situ and in real time (e.g., for neural blockade), and / or obtain feedback to verify functionality of the implanted device over the life of the device, disease, and / or patient.

[0105] In some embodiments, for example, the evaluation / modulation assembly 312 (FIG. 3A) is part of an implantable device separate from the catheter shaft 308 to allow for continued use of the evaluation / modulation assembly 312 over an extended period of time (i.e., not just during a procedure). For example, the implantable device can include a microstimulation / modulation section (e.g., evaluation / modulation section 312 with electrodes 344) that is permanently or semi-permanently implanted at the treatment site and a hermetically sealed or mechanically sealed controller coupled to the implantable device. In various embodiments, the implantable device can include a variable resistive element, a variable capacitive element, one or more electrodes, and / or a fixed or anchoring element that positions the electrodes relative to tissue within the target site (e.g., within the nasal cavity).

[0106] In various embodiments, the implanted device is wirelessly powered by an external unit spaced apart from the monitoring and treatment assembly and treatment site. For example, the external power unit can be worn by the patient, implanted (e.g., subcutaneously, intracavitary, etc.) within the patient separate from the monitoring and treatment assembly, and / or otherwise spaced apart from the treatment site. The device may have a battery-independent power source to avoid further clinical intervention. For example, the device may use capacitive coupling to charge / receive transient charges and / or generation of a magnetic field to couple to the power unit. In some embodiments, magnetic resonance coupling may be the connection mechanism for wireless / battery connectivity and coupling.

[0107] The implanted device treats conditions such as rhinitis by electrically modulating the parasympathetic pathways to the nasal cavity in a manner similar to system 300 described above with reference to FIGS. 3A-3B, but may provide neuromodulation and / or anatomical mapping over an extended period of time (e.g., outside of a procedure) and may be activated upon the onset of a predefined sensed trigger (e.g., mucus gland or parasympathetic hyperactivity). For example, in some embodiments, modulation may be delivered in bursts in response to a threshold level of autonomic activity. In some embodiments, modulation may be delivered by the patient in response to a symptom state associated with a disease state (e.g., hay fever triggers, allergy symptoms as perceived by the patient such as sneezing, excessive nasal drip, nasal congestion, etc.). The modulation provided by the implanted device may selectively stimulate or modulate parasympathetic fibers, sympathetic fibers, sensory fibers, alpha / beta / delta fibers, C fibers, anoxic terminals of one or more of the above that are insulated on the outside of non-insulated fibers (areas having fibers), and / or other neural structures. In some embodiments, the implantable device may selectively target specific cells or cell regions, such as smooth muscle cells, submucosal glands, goblet cells, stratified cell regions within the nasal mucosa, etc. These target sites may be identified prior to implantation of the device, during implantation, and / or during anatomical mapping of neural structures and / or other tissues while the device is implanted.

[0108] The implantable device may be deployed to a target site via a delivery system (e.g., a catheter) using anatomical mapping (including neural mapping) for targeting and location accuracy as described above. For example, the delivery system may position and retrieve the implantable device on the nasal mucosa, partially within the nasal mucosa, or completely into the nasal mucosa. The delivery system may be spring-loaded, piston-actuated, hydraulically actuated, and / or otherwise actuated to deploy the implantable device from a distal end of the delivery system. When the implantable device is configured to be positioned or otherwise secured at least partially below the surface of the nasal wall, the delivery system may include an aspiration tip, a needle tip, a dissecting tip, a retractable blade having a rotating member / action, and / or other sharp structure capable of forming an opening and an insertion path into the soft tissue.

[0109] The implant delivery system may further include a linkage or coupling connecting the distal end portion of the delivery system (including the deployment and access components) to the proximal handle of the delivery system. The deployment of the implanted device from the delivery system may be driven by a slider, piston, push button, rotating element, and / or other actuator in the proximal handle that advances or initiates the implantation mechanism of the delivery system. In some embodiments, the delivery system may have a range / stroke limiting mechanism and / or other limiting features to limit insertion depth. In some embodiments, the delivery system may have suction features to control the tissue / device interface and the entry angulation of the implant. In some embodiments, the delivery system has angular / circumferential orientation control to selectively position the entry point of the implant. The delivery system may also have micro-location capabilities to fine-tune location accuracy based on neural location. In some embodiments, the distal tip of the implanted device is electrically coupled to the delivery system when the implanted device is in the delivery state (prior to deployment), acting independently or in conjunction with other features of the delivery system to provide further neural mapping and measurement features and improve location accuracy. In various embodiments, the evaluation / modulation assembly 312 (FIG. 3A) and the device 302 (FIG. 3A) can include features similar to those described above with respect to the implantable device and delivery system.

[0110] The neural and anatomical mapping systems, devices, and methods disclosed herein can also be used with respect to additional disease states, including extranasal anatomical structures, and / or any peripheral nervous system acute or chronic disease state. The technology may be used to evaluate and / or monitor (short-term and / or long-term) neural / neuromuscular degenerative disease states, intraoperative neuroma continuity, and nerve regeneration and degenerative neuromuscular disorders. Other exemplary disease states treatable with the technology include acute inflammatory demyelinating polyneuropathy ("AIDP"), multiple sclerosis ("MS"), acute motor axonal neuropathy ("MAN"), Lambert-Eaton myasthenic syndrome ("LEMS"), myasthenia gravis ("MG"), neuromuscular transmission disorders ("NMTD"), peripheral neurophysiological testing ("PNE"), neuromuscular transmission disorders of any nerve terminal function, transmitter generation, storage, and / or release, pre- and post-synaptic membrane structure and function, receptor dynamics, endplate potentials, propagating muscle action potentials, and others.

[0111] Additional Examples Several aspects of the present technology are described in the additional examples below. 1. A system for detecting anatomical structures and therapeutic neuromodulation in the nasal region of a human patient, comprising: a shaft having a proximal portion and a distal portion, the distal portion configured to be positioned intraluminally at a target site within a nasal cavity below the sphenopalatine foramen of a human patient; an evaluation / modulation assembly in a distal portion of the shaft, the evaluation / modulation assembly including a plurality of electrodes configured to emit stimulation energy to tissue at a target site at a frequency for locating a target neural structure and to detect bioelectrical properties in response to the stimulation energy; A system comprising: a console, the controller having a computer readable medium carrying instructions that, when executed by a controller, cause the console to map locations of target neural structures and cause an evaluation / modulation assembly to apply therapeutic neuromodulation energy in a predetermined neuromodulation pattern based on the locations of the target neural structures. 2. The system of Example 1, wherein at least a portion of the plurality of electrodes are configured to apply RF energy at a predetermined frequency to initiate ionic agitation of targeted neural structures to therapeutically modulate postganglionic parasympathetic nerves. 3. The system of Example 1 or 2, wherein at least a portion of the plurality of electrodes are configured to apply RF energy at a predetermined frequency to initiate ionic agitation of submucosal structures to therapeutically modulate postganglionic parasympathetic tone. 4. A system as described in any one of Examples 1 to 3, wherein at least a portion of the plurality of electrodes are configured to apply RF energy at a predetermined frequency to initiate vacuolar degeneration of a targeted neural structure to therapeutically modulate postganglionic parasympathetic nerves. 5. a plurality of electrodes configured to detect bioelectrical properties of non-target anatomical structures at the target site; The system of any one of Examples 1 to 4, wherein the computer-readable medium carries instructions that, when executed by the controller, cause the console to map the locations of non-target anatomical structures and cause the evaluation / modulation assembly to apply neuromodulation energy in a predetermined pattern to avoid the locations of the non-target anatomical structures. 6. A system described in any one of Examples 1 to 5, further comprising a display configured to visualize the location of a target neural structure with respect to a predicted neuromodulation zone defined by the predetermined neuromodulation pattern. 7. The system of any one of Examples 1-6, wherein the plurality of electrodes are configured to detect bioelectrical properties of tissue at the treatment site prior to, during, and / or after therapeutic neuromodulation. 8. The system of example 7, wherein the bioelectrical property includes at least one of complex impedance, resistance, reactance, capacitance, inductance, dielectric constant, conductivity, nerve firing voltage, nerve firing current, magnetic field, and induced electromotive force. 9. Evaluation / Modulation Assembly a basket deformable between a low-profile delivery state and an expanded state, the basket including a plurality of struts radially spaced apart from one another when the basket is in the expanded state; A plurality of electrodes are disposed on the support; the plurality of struts are configured to position at least two of the electrodes at the target site when the basket is in the expanded state; The system of any one of Examples 1 to 8, wherein the electrode is configured to apply radio frequency (RF) energy to the target site to therapeutically modulate parasympathetic nerves proximate the target site. 10. Evaluation / modulation assembly The system described in Example 9, further comprising an expandable member within the basket, the expandable member being transformable between a low-profile delivery state to an expanded state, and at least a portion of the plurality of electrodes being disposed on an outer surface of the expandable surface. 11. The system of example 10, wherein the balloon comprises a plurality of holes configured to allow perfusion of an agent through the balloon when the balloon is in an expanded state. 12. Evaluation / modulation assembly an expandable member within the basket, the expandable member being transformable between a low-profile delivery state to an expanded state; The system of Example 9, further comprising at least one sensing electrode disposed on the expandable member, the sensing electrode defining a coil shape extending around a circumferential portion of the expandable member. 13. The evaluation / modulation assembly an expandable member within the basket, the expandable member being transformable between a low-profile delivery state to an expanded state; The system described in Example 9, further comprising a plurality of penetrating electrodes disposed on an outer surface of the expandable member, the expandable member being configured to position at least a portion of the penetrating electrodes at a fixed depth into tissue at the target site when the expandable member is in an expanded state. 14. A system described in any one of Examples 1 to 13, wherein the plurality of electrodes includes an array of penetrating electrodes configured to penetrate a fixed depth into tissue at the target site when the expandable member is in an expanded state. 15. The system of example 14, wherein the penetrating electrode is configured to detect muscle contraction in response to stimulation energy. 16. A system described in any one of Examples 1 to 15, wherein the evaluation / modulation assembly comprises a balloon transformable between a low-profile delivery state and an expanded state, and at least a portion of the plurality of electrodes are disposed on the balloon. 17. A system described in any one of Examples 1 to 16, wherein multiple electrodes are configured to be independently actuated and independently assigned selective polarity to apply therapeutic neuromodulation across selected regions of the evaluation / modulation assembly. 18. A system for detecting anatomical structures and therapeutic neuromodulation in the nasal region of a human patient, comprising: a shaft having a proximal portion and a distal portion, the shaft configured to position the distal portion within a lumen at a target site, the target site being at least one of adjacent to or below the sphenopalatine foramen of a human patient; an evaluation / modulation assembly at a distal portion of the shaft and transformable between a low-profile delivery state and an expanded state, the evaluation / modulation assembly comprising a plurality of electrodes configured to be placed in contact with tissue at a target site when the evaluation / modulation assembly is in the expanded state and to measure bioelectrical properties of the tissue at the target site to identify and locate target anatomical structures and non-target structures; A system comprising: a console, the controller having a computer readable medium carrying instructions that, when executed by a controller, cause the console to map locations of target anatomical structures and non-target anatomical structures, and cause an evaluation / modulation assembly to apply therapeutic neuromodulation energy in a predetermined neuromodulation pattern based on the locations of the target and non-target anatomical structures. 19. The system of example 18, wherein the instructions, when executed by the controller, cause the evaluation / modulation assembly to determine a resistance at least proximate to the target site. 20. The system of Example 18 or 19, wherein the bioelectrical properties are detected before, during, and / or after therapeutic neuromodulation, and the bioelectrical properties include at least one of complex impedance, resistance, reactance, capacitance, inductance, dielectric constant, conductivity, nerve firing voltage, nerve firing current, magnetic field, and induced electromotive force. 21. A system described in any one of Examples 18 to 20, wherein at least a portion of the plurality of electrodes are configured to apply RF energy at a predetermined frequency to activate a target anatomical structure for anatomical mapping and / or therapeutic neuromodulation. 22. The evaluation / modulation assembly a frame deformable between a low-profile delivery state and an expanded state, the frame including a plurality of struts radially spaced apart from one another when the frame is in the expanded state; A plurality of electrodes are disposed on the support; The system of Examples 18 to 21, wherein the multiple struts are configured to position at least two of the electrodes at the target site when the frame is in an expanded state. 23. The system described in Examples 18-22, wherein the evaluation / modulation assembly comprises an expandable member that is deformable between a low-profile delivery state to an expanded state, and at least a portion of the plurality of electrodes are disposed on the expandable member. 24. A method for therapeutically modulating nerves in the nasal region of a human patient, comprising: advancing an evaluation / modulation assembly on a distal portion of a shaft of the treatment device within the lumen to a target site in the nasal region, the target site being proximate to a parasympathetic nerve, the evaluation / modulation assembly including a plurality of electrodes; delivering stimulation energy to a target site to activate neural structures at the target site, the stimulation energy being emitted at one or more frequencies to locate specific target neural structures; Detecting one or more bioelectrical parameters at the target site via at least a portion of a plurality of electrodes of the evaluation / modulation assembly; determining a relative presence and location of a target neural structure at the target site based on the detected bioelectrical parameters; determining a neuromodulation pattern based on a location of the target neural structure and blocking the detected target neural structure. 25. The method of example 24, further comprising delivering therapeutic neuromodulation energy based on a predetermined neuromodulation pattern. 26. The method of Example 25, wherein delivering therapeutic neuromodulation energy further comprises delivering RF energy at a predetermined frequency to initiate ionic agitation of the targeted neural structure to therapeutically modulate postganglionic parasympathetic nerves. 27. The method of Example 25, wherein delivering therapeutic neuromodulation energy further comprises delivering RF energy at a predetermined frequency to initiate ionic agitation of submucosal structures to therapeutically modulate postganglionic parasympathetic nerves. 28. The method of example 25, wherein delivering therapeutic neuromodulation energy further comprises delivering RF energy at a predetermined frequency to initiate vacuolar degeneration of the targeted neural structure to therapeutically modulate postganglionic parasympathetic nerves. 29. The method of any one of Examples 24-28, wherein detecting one or more bioelectrical parameters comprises detecting the resistance of tissue. 30. The method of any one of Examples 24-29, wherein detecting one or more bioelectrical parameters includes detecting at least one of a nerve firing voltage and a nerve firing current. 31. The method of any one of Examples 24-30, wherein detecting one or more bioelectrical parameters comprises detecting a neuromagnetic field at the target site. 32. The method of any one of Examples 24-31, wherein detecting one or more bioelectrical parameters comprises detecting an induced electromotive force at the target site. 33. detecting one or more bioelectrical parameters at the target site includes detecting bioelectrical parameters of non-target anatomical structures at the target site; The method of any one of Examples 24-32, wherein the method further comprises locating non-target structures in the target site based on the detected bioelectrical parameters. 34. The method of any one of Examples 24 to 33, further comprising visually mapping the location of the target neural structure with respect to a predicted neuromodulation zone defined by the predetermined neuromodulation pattern. 35. The method of any one of Examples 24 to 34, further comprising deploying an array of penetrating electrodes such that at least a portion of the penetrating electrodes penetrate a certain depth into the target tissue prior to delivering the stimulation energy, the penetrating electrodes being at least a portion of a plurality of electrodes and disposed on the evaluation / modulation assembly. 36. Sensing one or more bioelectrical parameters at the target site via at least a portion of the plurality of electrodes of the evaluation / modulation assembly includes detecting muscle contraction data in response to stimulation energy via the penetrating electrodes; The method of Example 35, wherein identifying the relative presence and location of the target neural structure at the target site comprises mapping the location of the target neural structure based on the detected muscle contraction data. 37. A method for therapeutically modulating nerves in the nasal region of a human patient, comprising: endoluminally advancing an evaluation / modulation assembly on a distal portion of a shaft of a treatment device to a target site in a nasal region, the target site being proximate a parasympathetic nerve, the evaluation / modulation assembly including a plurality of electrodes; prior to therapeutic neuromodulation, detecting one or more baseline bioelectrical parameters at the target site via at least a portion of the plurality of electrodes; Geometrically identifying unique tissue characteristics within the target site based on the detected bioelectrical parameters to locate the target and non-target structures; determining a neuromodulation pattern based on the location of the target structure and the non-target structure; and delivering therapeutic neuromodulation energy to the target structure according to the neuromodulation pattern. 38. determining, via the evaluation / modulation assembly, a bioelectrical parameter during one or more procedures during delivery of the therapeutic neuromodulation energy; The method of Example 37, further comprising determining, via the evaluation / modulation assembly, one or more post-procedure bioelectrical parameters following delivery of the therapeutic neuromodulation energy to determine the effectiveness of the delivery of the therapeutic neuromodulation energy in blocking the nerves that received the therapeutic neuromodulation energy. 39. The method of embodiment 37 or 38, wherein geometrically identifying unique tissue properties within the target site based on the detected bioelectrical parameters comprises detecting neural firing rates at the target site. 40. The method of any one of Examples 37-39, wherein delivering therapeutic neuromodulation energy to the target structure in accordance with a neuromodulation pattern comprises delivering RF energy at a predetermined frequency to initiate ionic agitation of the target structure to therapeutically modulate postganglionic parasympathetic nerves. 41. The method of any one of Examples 37-40, wherein delivering therapeutic neuromodulation energy to the target structure in accordance with a neuromodulation pattern comprises delivering RF energy at a predetermined frequency to initiate ionic agitation of the submucosal structures to therapeutically modulate postganglionic parasympathetic nerves. 42. The method of any one of Examples 37 to 41, wherein delivering therapeutic neuromodulation energy to the target structure in accordance with a neuromodulation pattern comprises delivering RF energy at a predetermined frequency to initiate vacuolar degeneration of the target structure to therapeutically modulate postganglionic parasympathetic nerves. 43. A device for detecting anatomical structures and therapeutic neuromodulation in the nasal region of a human patient, the system comprising: a shaft having a proximal portion and a distal portion, the distal portion configured to be positioned intraluminally at a target site within a nasal cavity below the sphenopalatine foramen of a human patient; an evaluation / modulation assembly at a distal portion of the shaft, the evaluation / modulation assembly includes a plurality of electrodes configured to emit stimulation energy to tissue at the target site at frequencies for locating the target structure and non-target structures, and to detect bioelectrical properties in response to the stimulation energy; The bioelectrical properties are used to map the location of the target and non-target structures; and an evaluation / modulation assembly, wherein at least a portion of the plurality of electrodes are configured to apply therapeutic neuromodulation energy in a predetermined neuromodulation pattern based on the location of the target and non-target structures. 44. The device of Example 43, wherein at least a portion of the plurality of electrodes are configured to apply RF energy at a predetermined frequency to initiate ionic agitation and / or vacuolar degeneration of targeted structures to therapeutically modulate postganglionic parasympathetic nerves.

[0112] conclusion This disclosure is not intended to be exhaustive or to limit the technology to the precise forms disclosed herein. Although specific embodiments are disclosed herein for illustrative purposes, it will be understood by those skilled in the art that various equivalent modifications are possible without departing from the technology. In some cases, well-known structures and functions have not been shown and / or described in detail to avoid unnecessarily obscuring the description of the embodiments of the technology. Although steps of a method may be presented herein in a specific order, in alternative embodiments, the steps may have another suitable order. Similarly, certain aspects of the technology disclosed in the context of certain embodiments may be combined or omitted in other embodiments. Furthermore, although advantages associated with certain embodiments may be disclosed in the context of those embodiments, other embodiments may also exhibit such advantages, and not all embodiments necessarily exhibit such advantages or other advantages disclosed herein to fall within the scope of the technology. Thus, this disclosure and related technology may encompass other embodiments not explicitly shown and / or described herein.

[0113] Throughout this disclosure, the singular terms "a," "an," and "the" include plural referents unless the context clearly indicates otherwise. Similarly, unless the word "or" is expressly limited in relation to a list of two or more items to mean only a single item exclusively from the other items, then the use of "or" with such a list should be interpreted as including (a) any single item in the list, (b) all items in the list, or (c) any combination of items in the list. Furthermore, terms such as "comprise" are used throughout this disclosure to mean including at least the recited feature(s), and thus do not exclude any greater number of the same feature(s) and / or one or more additional types of features. Directional terms such as "upper," "lower," "forward," "backward," "vertical," and "horizontal" may be used herein to express and clarify the relationship between various elements. Of course, such terms do not imply an absolute orientation. References herein to "one embodiment," "an embodiment," or similar formalizations mean that a particular feature, structure, operation, or characteristic described in connection with an embodiment can be included in at least one embodiment of the technology. Thus, appearances of such phrases or formalizations herein are not necessarily all referring to the same embodiment. Furthermore, various particular features, structures, operations, or characteristics may be combined in any suitable manner in one or more embodiments.

Claims

1. 1. A system for detecting anatomical structures and therapeutic neuromodulation in a nasal region of a human patient, comprising: a shaft having a proximal portion and a distal portion, the shaft being configured to position the distal portion intraluminally at a target site within a nasal cavity below the sphenopalatine foramen of the human patient; an evaluation / modulation assembly at the distal portion of the shaft, the evaluation / modulation assembly comprising a plurality of electrodes configured to emit stimulation energy to tissue at the target site at at least two different frequencies for locating a target neural structure, the evaluation / modulation assembly configured to detect resultant bioelectrical properties in response to the stimulation energy and to detect baseline bioelectrical properties without the emission of the stimulation energy; a console, the controller having a computer readable medium carrying instructions that, when executed by a controller, cause the console to: (1) identify a location of the target neural structure based on the detected bioelectrical characteristic and the baseline bioelectrical characteristic; and (2) generate an ablation pattern based on the identified location of the target neural structure, the ablation pattern including an area of ​​influence of each of the plurality of electrodes, and cause the evaluation / modulation assembly to apply therapeutic neuromodulation energy in accordance with the generated ablation pattern.

2. 10. The system of claim 1, wherein at least a portion of the plurality of electrodes are configured to apply RF energy at a predetermined frequency to initiate ionic agitation of the target neural structures to therapeutically modulate postganglionic parasympathetic nerves.

3. 10. The system of claim 1, wherein at least a portion of the plurality of electrodes are configured to apply RF energy at a predetermined frequency to initiate ionic agitation of submucosal structures to therapeutically modulate postganglionic parasympathetic tone.

4. 10. The system of claim 1, wherein at least a portion of the plurality of electrodes are configured to apply RF energy at a predetermined frequency to initiate vacuolar degeneration of the target neural structure to therapeutically modulate postganglionic parasympathetic nerves.

5. the plurality of electrodes are configured to detect bioelectrical properties of non-target anatomical structures at the target site; 2. The system of claim 1, wherein the computer readable medium carries instructions that, when executed by the controller, cause the console to identify locations of the non-target anatomical structures and cause the evaluation / modulation assembly to apply neuromodulation energy according to the generated ablation pattern to avoid the locations of the non-target anatomical structures.

6. 10. The system of claim 1, further comprising a display configured to visualize a location of the target neural structure with respect to a predicted neuromodulation zone defined by the generated ablation pattern.

7. 10. The system of claim 1, wherein the plurality of electrodes are configured to detect bioelectrical properties of tissue at the target site before, during, and / or after therapeutic neuromodulation.

8. 8. The system of claim 7, wherein the bioelectrical property comprises at least one of a complex impedance, a resistance, a reactance, a capacitance, an inductance, a dielectric constant, a conductivity, a nerve firing voltage, a nerve firing current, a magnetic field, and an induced electromotive force.

9. said evaluation / modulation assembly comprising: a basket deformable between a low-profile delivery state and an expanded state, the basket including a plurality of struts radially spaced apart from one another when the basket is in the expanded state; the plurality of electrodes are disposed on the support; the plurality of struts are configured to position at least two of the electrodes at the target site when the basket is in the expanded state; The system of claim 1 , wherein the electrodes are configured to apply radio frequency (RF) energy to the target site to therapeutically modulate parasympathetic nerves proximate the target site.

10. said evaluation / modulation assembly comprising:

10. The system of claim 9, further comprising an expandable member expandable within the basket and deformable between a low-profile delivery state to an expanded state, at least a portion of the plurality of electrodes being disposed on an outer surface of the expandable member.

11. 2. The system of claim 1, wherein the evaluation / modulation assembly comprises a balloon deformable between a low-profile delivery state to an expanded state, the balloon comprising a plurality of holes configured to allow perfusion of an agent through the balloon when the balloon is in the expanded state.

12. said evaluation / modulation assembly comprising: an expandable member within the basket, the expandable member being transformable between a low-profile delivery state to an expanded state; 10. The system of claim 9, further comprising: at least one sensing electrode disposed on the expandable member, the sensing electrode defining a coil shape extending around a circumferential portion of the expandable member.

13. said evaluation / modulation assembly comprising: an expandable member within the basket, the expandable member being transformable between a low-profile delivery state to an expanded state; 10. The system of claim 9, further comprising: a plurality of penetrating electrodes disposed on an outer surface of the expandable member, the expandable member configured to position at least a portion of the penetrating electrodes at a fixed depth into tissue at the target site when the expandable member is in the expanded state.

14. 2. The system of claim 1, comprising an expandable member deformable between a low-profile delivery state to an expanded state, the plurality of electrodes including an array of penetrating electrodes configured to penetrate a constant depth into tissue at the target site when the expandable member is in the expanded state.

15. The system of claim 14 , wherein the penetrating electrode is configured to detect muscle contractions in response to the stimulation energy.

16. The system of claim 1 , wherein the evaluation / modulation assembly comprises a balloon deformable between a low-profile delivery state and an expanded state, and at least a portion of the plurality of electrodes are disposed on the balloon.

17. 2. The system of claim 1, wherein the multiple electrodes are configured to be independently actuated and assigned independently selective polarities to apply therapeutic neuromodulation across selected regions of the evaluation / modulation assembly.

18. 1. A system for detecting anatomical structures and therapeutic neuromodulation in a nasal region of a human patient, comprising: a shaft having a proximal portion and a distal portion, the shaft configured to position the distal portion intraluminally at a target site, the target site being at least one of adjacent to or inferior to the sphenopalatine foramen of a human patient; an evaluation / modulation assembly at the distal portion of the shaft and transformable between a low profile delivery state and an expanded state, the evaluation / modulation assembly comprising a plurality of electrodes configured to be placed in contact with tissue at the target site when the evaluation / modulation assembly is in the expanded state and to emit stimulation energy to tissue at the target site at at least two different frequencies for locating target neural structures, the evaluation / modulation assembly configured to detect resultant bioelectrical properties of tissue at the target site in response to the stimulation energy and to detect baseline bioelectrical properties without the emission of the stimulation energy, and to detect target anatomical structures and non-target structures; a console including a controller having a computer readable medium carrying instructions that, when executed by a controller, cause the console to: (1) identify locations of the target anatomical structures and non-target anatomical structures based on the detected bioelectrical properties and the baseline bioelectrical properties; and (2) generate an ablation pattern based on the identified locations of the target anatomical structures and non-target anatomical structures, the ablation pattern including an area of ​​influence of each of the plurality of electrodes; and cause the evaluation / modulation assembly to apply therapeutic neuromodulation energy in accordance with the generated ablation pattern.

19. The system of claim 18 , wherein the instructions, when executed by the controller, cause the evaluation / modulation assembly to determine a resistance proximate to at least the target site.

20. 20. The system of claim 18, wherein the bioelectrical properties are detected before, during, and / or after therapeutic neuromodulation, and the bioelectrical properties include at least one of complex impedance, resistance, reactance, capacitance, inductance, dielectric constant, conductivity, nerve firing voltage, nerve firing current, magnetic field, and induced electromotive force.

21. 20. The system of claim 18, wherein at least a portion of the plurality of electrodes are configured to apply RF energy at a predetermined frequency to activate a target anatomical structure for localization and / or therapeutic neuromodulation.

22. said evaluation / modulation assembly comprising: a frame deformable between the low-profile delivery state and the expanded state, the frame including a plurality of struts radially spaced apart from one another when the frame is in the expanded state; the plurality of electrodes are disposed on the support; The system of claim 18 , wherein the plurality of struts are configured to position at least two of the electrodes at the target site when the frame is in the expanded state.

23. 20. The system of claim 18, wherein the evaluation / modulation assembly comprises an expandable member that is deformable between the low-profile delivery state and the expanded state, and at least a portion of the plurality of electrodes are disposed on the expandable member.

24. A device for detecting anatomical structures and therapeutic neuromodulation in the nasal region of a human patient, the system comprising: a shaft having a proximal portion and a distal portion, the shaft being configured to position the distal portion intraluminally at a target site within a nasal cavity below the sphenopalatine foramen of the human patient; an evaluation / modulation assembly at the distal portion of the shaft, the evaluation / modulation assembly includes a plurality of electrodes configured to emit stimulation energy into tissue at the target site at at least two different frequencies for locating target and non-target structures, and configured to detect resultant bioelectrical properties in response to the stimulation energy and detect baseline bioelectrical properties without the emission of the stimulation energy; the bioelectrical characteristic and the baseline bioelectrical characteristic are used to identify the location of the target structure and the non-target structure; the identified locations are used to generate an ablation pattern based on the locations of the target structure and the non-target structures, the ablation pattern including an area of ​​influence of each of the plurality of electrodes; an evaluation / modulation assembly, wherein at least a portion of the plurality of electrodes are configured to apply therapeutic neuromodulation energy according to the generated ablation pattern.

25. 25. The device of claim 24, wherein at least a portion of the plurality of electrodes are configured to apply RF energy at a predetermined frequency to initiate ionic agitation and / or vacuolar degeneration of the target structures to therapeutically modulate postganglionic parasympathetic nerves.

Images