Devices and related methods and systems for therapeutic nasal neuromodulation

Abstract

To disclose herein devices for therapeutic nasal neuromodulation and associated methods and systems.SOLUTION: A system for therapeutic neuromodulation in a nasal region configured in accordance with embodiments of the present technology can include, for example, a shaft and a therapeutic element at a distal portion of the shaft. The shaft can locate the distal portion intraluminally at a target site inferior to a patient's sphenopalatine foramen. The therapeutic element can include an energy delivery element configured to therapeutically modulate postganglionic parasympathetic nerves at microforamina of a palatine bone of the human patient for the treatment of rhinitis or other indications. In other embodiments, the therapeutic element can be configured to therapeutically modulate nerves that innervate the frontal, ethmoidal, sphenoidal, and maxillary sinuses for the treatment of chronic sinusitis.SELECTED DRAWING: Figure 1A

Description

[Technical Field]

[0001] [CROSS-REFERENCE TO RELATED APPLICATIONS] This application claims priority to U.S. Provisional Patent Application No. 62 / 160,289, filed May 12, 2015, which is incorporated by reference herein in its entirety.

[0002] [Technical field] The present technology relates generally to devices, systems, and methods for therapeutically modulating nerves within or associated with a patient's nasal region. Specifically, various embodiments of the technology relate to therapeutic neuromodulation systems and methods for treating rhinitis and other conditions. [Background technology]

[0003] Rhinosinusitis is characterized by 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., rhinorrhoea and / or postnasal drip), facial pain, facial pressure, and / or reduced or lost sense of smell. Allergic rhinitis may include additional symptoms such as sneezing, watery rhinorrhea, nasal itching, and itchy or watery eyes. Severe rhinitis can lead to complicated asthma flare-ups, sleep disturbances, and reduced daily activities. Depending on the interval and type of system, rhinosinusitis can be divided into four subtypes: acute rhinosinusitis, recurrent rhinosinusitis, chronic rhinosinusitis with nasal polyps (i.e., soft, noncancerous growths inside the nostrils or sinuses), and chronic rhinosinusitis without nasal polyps. 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 rhinosinusitis refers to four episodes of acute rhinosinusitis within a 12-month period, with resolution of symptoms between each episode.

[0004] There are numerous environmental and biological causes of rhinosinusitis. For example, non-allergic rhinosinusitis can be caused by environmental irritants (e.g., exhaust steam, cleaning fluids, latex, fragrances, 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., environmental allergens that occur at the same time each year), perennial allergens that occur year-round (e.g., dust mites, animal dander, mold, etc.), and / or occupational allergens (e.g., certain chemicals, grains, latex, etc.).

[0005] Treatment for rhinosinusitis may include general avoidance of rhinitis triggers, nasal irrigation with saline solution, 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 higher than placebo) and undesirable side effects such as sedation, irritation, loss of taste, sore throat, dry nose, epistaxis (i.e., nosebleeds), and / or headache. 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 extended administration periods (e.g., 3-5 years for SLIT) and can result in numerous side effects, including pain and swelling at the site of injection, skin itching (i.e., hives), angioedema, asthma, and anaphylaxis.

[0006] Surgical intervention has also been used in attempts to treat patients with severe rhinitis symptoms resistant to medication. In the 1960s–1980s, surgical procedures were performed to cut parasympathetic nerve fibers within the alar canal to reduce parasympathetic tone in the nasal mucosa. More recent attempts at vidian nerve transection have been found to be 50–88% effective in treating rhinorrhea, with other concomitant benefits, including improvement in symptoms of sneezing and nasal obstruction. These symptomatic improvements also resulted in reductions in interstitial edema, eosinophilic cell infiltration, mast cell levels, and elimination. The reduction in histamine concentration in the neural mucosa correlated with histological mucosal changes. However, despite the clinical and histological efficacy of vidian nerve transection, resection of the vidian nerve failed to gain widespread acceptance, primarily due to the mortality associated with the loss of its anatomical and autonomic selectivity. For example, the neurectomy site contains preganglionic secretagogue fibers to the lacrimal gland; therefore, neurectomy often results in loss of the tear reflex, i.e., lacrimation, which in severe cases can lead to loss of vision. Due to such irreversible complications, this technique was prematurely abandoned. Furthermore, due to the passage of postganglionic pterygopalatine fibers through the retroorbital plexus, the location of the vidian nerve transection relative to the target end organ (i.e., the nasal mucosa) may result in reinnervation via the autonomic plexus and otic ganglion process that coexists with the accessory meningeal artery.

[0007] Complications associated with vidian neurectomy are largely due to the nonspecific location 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 neurectomy while avoiding secondary injury to the lacrimal gland and sympathetic nerve fibers. For example, Japanese surgeons are performing transnasal inferior turbinate submucosal resection along with resection of the posterior nasal nerve (PNN), a postganglionic nerve pathway further downstream from the vidian nerve. (See Kobayashi T, Hyodo M, Nakamura K, Komobuchi H, Honda N, Resection of peripheral branch 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, where the PNN is thought to enter the nasal region. These nerve transections are highly complex and laborious due to the lack of good surgical markers for identifying the desired posterior nasal nerve, and even once the desired nerve location is determined, resection is extremely difficult because the nerve must be separated from the surrounding vasculature (e.g., the sphenopalatine artery).

[0008] Many aspects of the present technology may be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale. Instead, emphasis is placed upon 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. [Brief explanation of the drawings]

[0009] [Figure 1A] FIG. 1 is a cutaway side view illustrating the anatomy of the nasal side wall.

[0010] [Figure 1B]FIG. 1B is an enlarged lateral view of the nerves in the lateral wall of the nose of FIG. 1A.

[0011] [Figure 1C] FIG. 1 is a front view of the left palate illustrating the geometry of the micropores within the left palate.

[0012] [Figure 2] FIG. 1 is a partial schematic diagram of a therapeutic neuromodulation system for therapeutically modulating nerves in the nasal region in accordance with an embodiment of the present technology.

[0013] [Figure 3A] 10A-10C are partial cutaway side views illustrating various approaches for delivering a distal portion of a therapeutic neuromodulation device to a target site within the nasal region in accordance with embodiments of the present technology. [Figure 3B] 10A-10C are partial cutaway side views illustrating various approaches for delivering a distal portion of a therapeutic neuromodulation device to a target site within the nasal region in accordance with embodiments of the present technology. [Figure 3C] 10A-10C are partial cutaway side views illustrating various approaches for delivering a distal portion of a therapeutic neuromodulation device to a target site within the nasal region in accordance with embodiments of the present technology. [Figure 3D] 10A-10C are partial cutaway side views illustrating various approaches for delivering a distal portion of a therapeutic neuromodulation device to a target site within the nasal region in accordance with embodiments of the present technology. [Figure 3E] 10A-10C are partial cutaway side views illustrating various approaches for delivering a distal portion of a therapeutic neuromodulation device to a target site within the nasal region in accordance with embodiments of the present technology.

[0014] [Figure 4] FIG. 10 is an isometric view of a distal portion of a therapeutic neuromodulation device configured in accordance with an embodiment of the present technology.

[0015] [Figure 5A] FIG. 10 is an isometric view of an electrode configuration of a therapeutic neuromodulation device for therapeutic neuromodulation in accordance with an embodiment of the present technology. [Figure 5B] FIG. 10 is an isometric view of an electrode configuration of a therapeutic neuromodulation device for therapeutic neuromodulation in accordance with an embodiment of the present technology. [Figure 5C] FIG. 10 is an isometric view of an electrode configuration of a therapeutic neuromodulation device for therapeutic neuromodulation in accordance with an embodiment of the present technology. [Figure 5D] FIG. 10 is an isometric view of an electrode configuration of a therapeutic neuromodulation device for therapeutic neuromodulation in accordance with an embodiment of the present technology. [Figure 5E] FIG. 10 is an isometric view of an electrode configuration of a therapeutic neuromodulation device for therapeutic neuromodulation in accordance with an embodiment of the present technology. [Figure 5F] FIG. 10 is an isometric view of an electrode configuration of a therapeutic neuromodulation device for therapeutic neuromodulation in accordance with an embodiment of the present technology. [Figure 5G] FIG. 10 is an isometric view of an electrode configuration of a therapeutic neuromodulation device for therapeutic neuromodulation in accordance with an embodiment of the present technology.

[0016] [Figure 6A] FIG. 10 is a partial schematic diagram illustrating an electrode configuration in a distal portion of a therapeutic neuromodulation device for neural sensing configured in accordance with an embodiment of the present technology. [Figure 6B] FIG. 10 is a partial schematic diagram illustrating an electrode configuration in a distal portion of a therapeutic neuromodulation device for neural sensing configured in accordance with an embodiment of the present technology.

[0017] [Figure 7] 1 is a graph illustrating threshold levels of electrical conductivity of nasal tissue with respect to temperature.

[0018] [Figure 8] FIG. 10 is an isometric view of a distal portion of a therapeutic neuromodulation device configured in accordance with an embodiment of the present technology. [Figure 9] FIG. 10 is an isometric view of a distal portion of a therapeutic neuromodulation device configured in accordance with an embodiment of the present technology.

[0019] [Figure 10A]FIG. 10 is an isometric view of a distal portion of a therapeutic neuromodulation device configured in accordance with another embodiment of the present technology. [Figure 10B] FIG. 10B is an isometric view illustrating the therapeutic neuromodulation device of FIG. 10A at a treatment site.

[0020] [Figure 11A] FIG. 10 is an isometric view illustrating a distal portion of a therapeutic neuromodulation device configured in accordance with yet another embodiment of the present technology. [Figure 11B] FIG. 10 is an isometric view illustrating a distal portion of a therapeutic neuromodulation device configured in accordance with yet another embodiment of the present technology. [Figure 11C] FIG. 10 is an isometric view illustrating a distal portion of a therapeutic neuromodulation device configured in accordance with yet another embodiment of the present technology. [Figure 11D] FIG. 10 is an isometric view illustrating a distal portion of a therapeutic neuromodulation device configured in accordance with yet another embodiment of the present technology.

[0021] [Figure 12] FIG. 10 is a side view of a distal portion of a therapeutic neuromodulation device configured in accordance with a further embodiment of the present technology.

[0022] [Figure 13] FIG. 10 is a side view of a distal portion of a therapeutic neuromodulation device configured in accordance with yet a further embodiment of the present technology.

[0023] [Figure 14] FIG. 10 is an isometric side view of a distal portion of a therapeutic neuromodulation device configured in accordance with an additional embodiment of the present technology.

[0024] [Figure 15] FIG. 10 is an isometric side view of a distal portion of a therapeutic neuromodulation device configured in accordance with an additional embodiment of the present technology.

[0025] [Figure 16] FIG. 10 is a side cross-sectional view of a distal portion of a therapeutic neuromodulation device configured in accordance with an additional embodiment of the present technology.

[0026] [Figure 17] FIG. 10 is a side cross-sectional view of a distal portion of a therapeutic neuromodulation device configured in accordance with an additional embodiment of the present technology.

[0027] [Figure 18] FIG. 10 is a side cross-sectional view of a distal portion of a therapeutic neuromodulation device configured in accordance with an additional embodiment of the present technology.

[0028] [Figure 19] FIG. 10 is a side view of a distal portion of a therapeutic neuromodulation device configured in accordance with an additional embodiment of the present technology.

[0029] [Figure 20] FIG. 10 is a partial cutaway side view illustrating a target site proximal to the ostium of a nasal sinus for a therapeutic neuromodulation device configured in accordance with an embodiment of the present technology. DETAILED DESCRIPTION OF THE INVENTION

[0030] The present technology generally relates to devices and related systems and methods for therapeutic nasal neuromodulation. The disclosed devices are configured to provide precise, localized, non-invasive energy application to disrupt parasympathetic motor and sensory function within the nasal region. Specific details of several embodiments of the present technology are described herein with reference to Figures 1A-20. While many of the embodiments are described with respect to devices, systems, and methods for therapeutically modulating nerves within the nasal region for the treatment of rhinitis, other applications and 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 treating other indications, such as treating chronic sinusitis and nosebleeds. It should be noted that other embodiments in addition to those described herein are within the scope of the present technology. Furthermore, embodiments of the present technology may have different configurations, components, and / or procedures than those shown or described herein. Moreover, those skilled in the art will understand that embodiments of the technology may have configurations, components, and / or procedures in addition to those shown or described herein, and that these and other embodiments may not involve some of the configurations, components, and / or procedures shown or described herein without departing from the technology.

[0031] With respect to the terms "distal" and "proximal" within this description, unless otherwise specified, these terms may refer to the location of a therapeutic neuromodulation device and / or portions of an associated delivery device relative to an operator and / or location within the nasal cavity. For example, with respect to a delivery catheter suitable for delivering and positioning the various prosthetic valve devices described herein, "proximal" may refer to a location closer to the operator of the device or the proximity of the entrance points of the patient's nostrils, and "distal" may refer to a location further from the operator of the device or further from the proximity of the entrance points of the patient's nostrils. In addition, posterior, anterior, inferior, and superior are used in standard It is used in accordance with the medical terminology.

[0032] As used herein, the terms "therapeutic modulation" and "therapeutic neuromodulation" of a nerve refer to the partial or complete disabling or other effective disruption of neural activity, including partial or complete ablation of a nerve. For example, therapeutic neuromodulation can include partially or completely inhibiting, reducing, and / or blocking neural transmission along a nerve fiber.

[0033] Nasal Cavity Anatomy Figure 1A is a cutaway lateral view illustrating the anatomy of the lateral wall of the nose, and Figure 1B is an enlarged lateral view of the nerves of the lateral wall of the nose of Figure 1A. The sphenopalatine foramen ("SPF," Figure 1A) is an opening or canal defined by the palatine and sphenoid bones through which the sphenopalatine vessels and posterior superior nasal nerve pass into the nasal cavity. More specifically, the orbital and sphenoidal processes of the perpendicular plates of the palatine bones define the sphenopalatine notch, which transforms into the SPF by articulation with the surface of the body of the sphenoid bone.

[0034] The location of the SPF is highly variable within the posterior region of the lateral nasal cavity, making it difficult to visually determine its location. Typically, the SPF is located within the middle meatus ("MM," Figure 1A). However, anatomical variations also result in the SPF being located within the superior meatus ("SM," Figure 1A) or at the junction between the superior and middle meatus. In certain individuals, for example, the inferior border of the SPF has been measured to be approximately 19 mm above the horizontal plate of the palatine bone (i.e., the nasal floor), approximately 13 mm above the horizontal lamina of the inferior turbinate ("IT," Figure 1A). The average distance from the nasal floor to the SPF is approximately 64.4 mm, resulting in an approach angle from the nasal floor to the SPF of approximately 11.4°. However, studies to measure the exact location of the SPF have limited practical use due to the high variability in its location.

[0035] Anatomical variations in the SPF are predicted to correspond to changes in the autonomic and vascular pathways traversing the nasal cavity. Generally, the posterior nasal nerve (also called the lateral posterior superior nasal nerve) branches from the pterygopalatine ganglion (PPG, also called the sphenopalatine ganglion; Figure 1A) and enters the lateral wall of the nasal cavity through the SPF. The sphenopalatine artery is thought to pass from the pterygopalatine fossa to the SPF on the lateral wall of the nose. The sphenopalatine artery branches into two main branches: the posterolateral nasal branch and the posterior septal branch. The main branch of the posterolateral nasal artery runs inferiorly into the inferior turbinate IT (e.g., approximately 1.0–1.5 mm from the posterior end of the inferior turbinate IT), and another branch enters the middle turbinate MT and branches anteriorly and posteriorly.

[0036] Beyond the SPF, studies have shown that over 30% of human patients have one or more accessory foraminae that also carry arteries and nerves into the nasal cavity. Accessory foramenae are typically smaller than the SPF and located below it. For example, there may be one, two, three, or more branches of the posterior nasal artery and posterior nasal nerve extending through the corresponding accessory foraminae. The variability in location, size, and quantity associated with accessory foraminae and the associated branching arteries and nerves that course through them creates considerable uncertainty regarding the location of the vasculature and nerves in the sphenopalatine region. Furthermore, the anatomy of the nerves extending from the SPF often includes deep inferior and / or superior grooves that carry the nerve and arterial pathways, making it difficult to determine the location of the arteries and nerve branches. For example, grooves may extend more than 5 mm in length, more than 2 mm in width, and more than 1 mm in depth, thereby creating a passage sufficient to carry both the artery and nerve. The variations caused by the grooves and accessory foramina in the sphenopalatine region make it extremely difficult for the surgeon to locate and access the arteries and nerves (located posterior to the arteries).

[0037] Recent microanatomical dissections of the pterygopalatine fossa (PPF) have further demonstrated the highly variable anatomy of the region surrounding the PPF, showing that numerous efferent branches projecting from the pterygopalatine ganglion ("PPG," Figure 1) innervate the orbital and nasal mucosa via numerous small nerve bundles rather than individual postganglionic autonomic nerves (e.g., the posterior nasal nerve). Studies have shown that at least 87% of humans have microforamina and microbranches within the palate. For example, Figure 1C is a frontal view of the left palate illustrating the geometry of microforamina and microbranches within the left palate. In Figure 1C, the filled areas represent nerves that traverse directly through the palate, while the open circles represent nerves associated with individual microforamina. Indeed, Figure 1C illustrates that the central portion of the palate may contain at least 25 accessory posterolateral nerves.

[0038] The respiratory portion of the nasal mucosa consists of a type of ciliated pseudostratified columnar epithelium with a basement membrane. Nasal secretions (e.g., mucus) are secreted by exudates from germ cells, submucosal glands, and plasma. The nasal septum and blood vessels are highly regulated by parasympathetic innervation derived from the vidian nerve and other nerves. Parasympathetic (cholinergic) stimulation through acetylcholine and vasoactive intestinal peptide generally leads to mucus production. Thus, parasympathetic innervation of the mucosa is primarily responsible for the activation / hyperactivation of submucosal glands, venous congestion (e.g., congestion), and increased blood flow to blood vessels within the nose. Therefore, ablation or modulation of the parasympathetic pathways innervating the mucosa is predicted to reduce or eliminate the hyperactivation of submucosal glands and vascular congestion that cause symptoms associated with rhinosinusitis and other conditions.

[0039] As mentioned above, postganglionic parasympathetic fibers innervating the nasal mucosa (i.e., the posterior superior nasal nerve) were thought to travel exclusively through the SPF as the sphenopalatine neurovascular bundle. The posterior nasal nerve is a branch of the maxillary nerve that innervates the nasal cavity via numerous smaller medial and lateral branches that extend through the mucosa of the superior turbinate ST and middle turbinate MT (i.e., nasal chonchea) to the nasal septum. The nasopalatine nerve is generally the largest of the medial posterior superior nasal nerves. It passes anteriorly and inferiorly within the supravomeral groove to the floor of the nasal cavity. From here, it passes through the incisive fossa of the hard palate and connects with the larger palatine nerve to supply the mucosa of the hard palate. The posterior superior nasal nerve passes through the pterygopalatine ganglion (PPG) without joining and passes over the maxillary nerve via its ganglionic branches.

[0040] Based on the understanding that the posterior nasal nerve exclusively crosses the SPF to innervate the nasal mucosa, surgical procedures have been performed to selectively cut the posterior nasal nerve as it exits the SPF. However, as discussed above, the parasympathetic pathway of the paranasal sinuses actually includes individual branches that emerge from the pterygopalatine ganglion (PPG) and innervate the nasal mucosa via multiple small nerve bundles (i.e., the accessory posterolateral nerve) rather than a single branch extending through the SPF. These branches communicate through multiple fissures, accessory foramina, and microforamina throughout the palate, and may demonstrate anastomosing rings involving both the SPF and other accessory nerves. Therefore, if only the parasympathetic nerves crossing the SPF are cut, nearly all patients (e.g., over 90%) will retain intact parasympathetic fibers to the posterolateral mucosa, which will result in the persistence of symptoms that nerve sectioning was intended to support.

[0041] Thus, embodiments of the present technology are configured to therapeutically modulate nerves at precise, focused treatment sites (e.g., target area T shown in FIG. 1B ) corresponding to the locations of branches extending through the fissures, accessory foramina, and microforamina throughout the palate. In certain embodiments, the targeted nerves are postganglionic parasympathetic nerves that travel to innervate the nasal mucosa. This selective nerve treatment is also expected to reduce the rate of postoperative nasal crusting and dryness, as it allows the clinician to gradually increase the degree of anterior denervation through careful avoidance of the orbital branches. Furthermore, embodiments of the present technology are also expected to preserve at least some sympathetic tone by preserving a portion of the sympathetic contribution from the deep petrosal nerve and the internal maxillary periarteriolar plexi, leading to improved outcomes with regard to nasal obstruction. Additionally, embodiments of the present technology are configured to target numerous parasympathetic nerve entry sites into the nasal region (e.g., accessory foramina, fissures, and microforamina) to provide complete resection of all anastomotic rings, thereby reducing the rate of long-term reinnervation.

[0042] Selected Embodiments of a System for Therapeutic Nasal Neuromodulation and Neural Mapping FIG. 2 is a partial schematic diagram of a therapeutic neuromodulation system 200 (“system 200”) for therapeutically modulating nerves in the nasal region in accordance with an embodiment of the present technology. System 200 includes a therapeutic neuromodulation catheter or device 202, a console 204, and a cable 206 extending therebetween. The therapeutic neuromodulation device 202 includes a shaft 208 having a proximal portion 208a and a distal portion 208b, a handle 210 at the proximal portion 208a of the shaft 208, and a therapeutic assembly or element 212 at the distal portion 208b of the shaft 208. Shaft 208 is configured for intraluminal placement of distal portion 208b at a treatment or target site in the nasal region proximal to postganglionic parasympathetic nerves that innervate the nasal mucosa. The target site may be a region, volume, or area in which a target nerve is located and may be of different sizes and shapes depending on the patient's anatomy. For example, the target site may be a 3 cm area below the SPF. In other embodiments, the target site may be larger, smaller, and / or located elsewhere within the nasal cavity to target desired nerve fibers. The treatment assembly 212 may include at least one energy delivery element 214 configured to therapeutically modulate postganglionic parasympathetic nerves. In certain embodiments, for example, the treatment assembly 212 may therapeutically modulate postganglionic parasympathetic nerves that branch from the pterygopalatine ganglion and innervate the nasal region and nasal mucosa, such as the parasympathetic nerves (e.g., the posterior nasal nerve) that traverse the SPF, accessory foramina, and microforamina of the palate bones.

[0043] As shown in FIG. 2 , the treatment assembly 212 includes at least one energy delivery element 214 configured to provide therapeutic neuromodulation to a target site. In certain embodiments, for example, the energy delivery element 214 may include one or more electrodes configured to apply electromagnetic neuromodulation energy (e.g., RF energy) to the target site. In other embodiments, the energy delivery element 214 may be configured to provide therapeutic neuromodulation using various other modalities, such as, for example, cryotherapeutic cooling, ultrasound energy (e.g., high-intensity focused ultrasound (“HIFU”) energy), microwave energy (e.g., via a microwave antenna), direct heating, high- and / or low-power laser energy, mechanical vibration, and / or optical power. In further embodiments, the treatment assembly 212 may be configured to deliver chemicals or drugs to the target site to chemically ablate or embolize the target nerve. For example, the treatment assembly 212 may include a needle applicator extending through the access portion of the shaft 208 and / or a separate introducer, which may be configured to inject a chemical substance, such as, for example, Botox, alcohol, guanethidine, ethanol, phenol, a neurotoxin, or another suitable agent that alters, damages, or disrupts nerves, into a target site to therapeutically modulate the target nerve.

[0044] In certain embodiments, the therapy assembly 212 may include one or more sensors (not shown), such as, for example, one or more temperature sensors (e.g., thermocouples, thermistors, etc.), impedance sensors, and / or other sensors. The sensor(s) and / or energy delivery element 214 may be connected to one or more wires (not shown, e.g., copper wires) extending through the shaft 208 to transmit signals to and / or from the sensor(s) and / or to conduct energy to the energy delivery element 214.

[0045] The therapeutic neuromodulation device 202 may be operatively coupled to the console 204 via a wired connection (e.g., via cable 206) and / or a wireless connection. The console 204 may be configured to control, monitor, deliver, and / or otherwise support the operation of the therapeutic neuromodulation device 202. The console 204 may be further configured to generate energy of a selected form and / or magnitude for delivery to tissue or nerves at a target site via the treatment assembly 212; thus, the console 204 may have different configurations depending on the treatment modality of the therapeutic neuromodulation device 202. For example, When the therapeutic neuromodulation device 202 is configured for electrode-based, thermal element-based, and / or transducer-based therapy, the console 204 may include an energy generator 216 configured to generate RF energy (e.g., monopolar, bipolar, or multipolar RF energy), pulsed electrical energy, microwave energy, light energy, ultrasound energy (e.g., intracavitary delivered ultrasound and / or HIFU), direct thermal energy, radiation (e.g., infrared, visible, and / or gamma radiation), and / or another suitable type of energy. When the therapeutic neuromodulation device 202 is configured for cryotherapeutic therapy, the console 204 may include a coolant reservoir (not shown) and may be configured to supply coolant to the therapeutic neuromodulation device 202. Similarly, when the therapeutic neuromodulation device 202 is configured for chemical-based therapy (e.g., drug infusion), the console 204 may include a chemical reservoir (not shown) and may be configured to supply one or more chemicals to the therapeutic neuromodulation device 202.

[0046] 2, the system 200 may further include a controller 218 communicatively coupled to the therapeutic neuromodulation device 202. In the illustrated embodiment, the controller 218 is housed within the console 204. In other embodiments, the controller 218 may be carried by the handle 210 of the therapeutic neuromodulation device 202, the cable 206, a separate component, and / or another portion of the system 200. The controller 218 may be configured to initiate, terminate, and / or regulate the operation of one or more components of the therapeutic neuromodulation device 202 (e.g., the energy delivery element 214) directly and / or via the console 204. The controller 218 may be configured to execute automatic control algorithms and / or receive control commands from an operator (e.g., a clinician). For example, the controller 218 and / or other components of the console 204 (e.g., memory) may include computer-readable media bearing instructions that, when executed by the controller 218, cause the treatment assembly 202 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 includes one or more of a variety of hardware devices for volatile and non-volatile storage and may include both read-only memory and writable memory. For example, memory may include random access memory (RAM), CPU registers, read-only memory (ROM), and writable non-volatile memory such as flash memory, hard drives, floppy disks, CDs, DVDs, magnetic storage devices, tape drives, device buffers, etc. Memory does not carry signals that are separate from the underlying hardware, and therefore, memory is non-transitory.

[0047] Additionally, the console 204 may be configured to provide feedback to the operator before, during, and / or after a therapeutic procedure via the evaluation / feedback algorithm 220. For example, the evaluation / feedback algorithm 220 may be configured to provide information related to the temperature of the tissue at the treatment site, the location of the nerves at the treatment site, and / or the effect of therapeutic neuromodulation on the nerves at the treatment site. In certain embodiments, the evaluation / feedback algorithm 220 may include features for confirming the effectiveness of the treatment and / or enhancing the desired performance of the system 200. For example, the evaluation / feedback algorithm 220, in conjunction with the controller 218, may be configured to monitor the temperature of the treatment site during therapy and automatically stop energy delivery when the temperature reaches a predetermined maximum value (e.g., during the application of RF energy) or a predetermined minimum value (e.g., during the application of cryotherapy). In other embodiments, the evaluation / feedback algorithm 220, in conjunction with the controller 218, may be configured to automatically terminate treatment after a predetermined maximum time, a predetermined maximum impedance rise in the targeted tissue (i.e., compared to a baseline impedance measurement), a predetermined maximum impedance in the targeted tissue, and / or other thresholds for biomarkers associated with autonomic function. This and other information associated with the operation of the system 200 is displayed on a display 222 (e.g., monitor) on the console 204. The information may be communicated to the operator via a separate display (not shown) communicatively coupled to the console 204.

[0048] In various embodiments, the treatment assembly 212 and / or other portions of the system 200 may be configured to detect various parameters of the heterogeneous tissue at the target site to determine the anatomical structure (e.g., tissue type, tissue location, vasculature, bony structures, foramen, sinuses, etc.) at the target site, determine the location of nerves and / or other structures, and enable neural mapping. For example, the treatment assembly 212 may be configured to detect impedance, dielectric properties, temperature, and / or other properties indicative of the presence of nerve fibers within the target region. As shown in FIG. 2 , the console 204 may include a neural monitoring assembly 221 (shown schematically) that receives detected electrical and / or thermal measurements of the tissue at the target site acquired by the treatment assembly 212 and process this information to identify the presence, location, and / or activity of nerves at the target site. This information may then be communicated to the operator via a high-resolution spatial grid and / or other type of display (e.g., on the display 222). The neuromonitoring assembly 221 may be operatively coupled to the energy delivery element 214 and / or other features of the treatment assembly 212 via a signal wire (e.g., copper wire) that runs through the cable 206 and through the length of the shaft 208. In other embodiments, the treatment assembly 212 may be communicatively coupled to the neuromonitoring assembly 221 using other suitable communication means.

[0049] The neuromonitoring assembly 221 can determine the location and activity of the nerve before therapeutic neuromodulation to determine the precise treatment area corresponding to the desired nerve location, determine the effectiveness of the therapeutic neuromodulation during treatment, and / or evaluate whether the therapeutic neuromodulation has treated the target nerve to the desired extent after treatment. This information can be used to make various decisions regarding the nerve proximal to the target site, such as whether the target site is suitable for neuromodulation. In addition, the neuromonitoring assembly 221 can also compare the 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. For example, the neuromonitoring assembly 221 can determine an electroneurogram (ENG) signal based on recordings of neuronal electrical activity acquired by the therapeutic assembly 212 before and after therapeutic neuromodulation. A statistically significant (e.g., measurable or noticeable) decrease in the ENG signal(s) acquired after neuromodulation can serve as an indicator that the nerve has been sufficiently ablated.

[0050] The system 200 may further include a channel 224 extending along at least a portion of the shaft 208 and a port 226 in the distal portion 208b of the shaft and in communication with the port 226. In certain embodiments, the channel 224 is a fluid pathway for delivering fluid to the distal portion 208b of the shaft 208 via the port 226. For example, the channel 224 may deliver saline solution or other fluid to rinse the nasal passages within the cavity during delivery of the treatment assembly 212, to flush the target site prior to application of 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 energy delivery element 214. In other embodiments, the channel 224 enables delivery of drugs to the treatment site. For example, a needle (not shown) may protrude through the port 226 to inject or otherwise deliver a nerve block, local anesthetic, and / or other pharmacological agent to tissue at the target site.

[0051] The therapeutic neuromodulation device 202 provides access to target sites deep within the nasal region, such as at the peripheral entrance of parasympathetic fibers into the nasal cavity, for therapeutically modulating autonomic activity within the nasal cavity. In certain embodiments, for example, the therapeutic neuromodulation device 202 may position the therapeutic assembly 212 below the SPF at the site of an access foramen and / or microforamen (e.g., as shown in FIGS. 1B and 1C). (As shown). By manipulating the proximal portion 208a of the shaft 208 from outside the nasal entrance, a clinician may advance the shaft 208 through the tortuous intraluminal passages and through the nasal cavity and remotely manipulate the distal portion 208b of the shaft 208 via the handle 210 to position the treatment assembly 212 at the target site. In certain embodiments, the shaft 208 may be a steerable device (e.g., a steerable catheter) having a small bend radius (e.g., a 5 mm bend radius, a 4 mm bend radius, a 3 mm bend radius, or less) that allows the clinician to navigate through the tortuous nasal anatomy. The steerable shaft may further be configured to articulate in at least two different directions. For example, the steerable shaft 208 may include dual pull wire rings that allow the clinician to form the distal portion 208b of the shaft 208 into an "S" shape to correspond to the anatomy of the nasal region. In other embodiments, the articulating shaft 208 may be made from a substantially rigid material (e.g., a metallic material) and may include a rigid link at the distal portion 208b of the shaft 208 that resists deflection but still allows for a small bend radius (e.g., a 5mm bend radius, a 4mm bend radius, a 3mm bend radius, or less). In a further embodiment, the steerable shaft 208 may be a laser-cut tube made from metal and / or other suitable material. The laser-cut tube may include one or more puller wires operated by a clinician to enable the clinician to deflect the distal portion 208b of the shaft 208 to navigate the intricate nasal anatomy to the target site.

[0052] In various embodiments, the distal portion 208b of the shaft 208 is guided to an appropriate position at the target site via a guidewire (not shown) using an over-the-wire (OTW) or rapid-exchange (RX) technique. For example, the distal end of the treatment assembly 212 may include a channel that engages the guidewire. Intraluminal delivery of the treatment assembly 212 may include inserting the guidewire into an orifice communicating with the nasal cavity (e.g., a nostril or mouth) and moving the shaft 208 and / or treatment assembly 212 along the guidewire until the treatment assembly 212 reaches the target site (e.g., below the SPF).

[0053] In further embodiments, the therapeutic neuromodulation device 202 may be configured for delivery via a guide catheter or introducer sheath (not shown), with or without the use of a guidewire. First, the introducer sheath may be inserted intraluminally to the target site within the nasal region, and then the distal portion 208b of the shaft 208 may be inserted through the introducer sheath. At the target site, the treatment assembly 212 may be deployed through the distal end opening or a side port of the introducer sheath. In certain embodiments, the introducer sheath may include a straight section and a pre-shaped section with a fixed curvature (e.g., a 5 mm curvature, a 4 mm curvature, a 3 mm curvature, etc.) that may be deployed intraluminally to approach the target site. In this embodiment, the introducer sheath may have a side port proximal to or along the pre-shaped curved section through which the treatment assembly 212 may be deployed. In other embodiments, the introducer sheath may be made of a rigid material, such as a metallic material coated with an insulating or dielectric material. In this embodiment, the introducer sheath is substantially straight and may be used to deliver the therapeutic assembly 212 to the target site via a substantially straight path, such as through the middle meatus MM (FIG. 1A).

[0054] Image guidance may be used to assist the clinician in positioning and manipulating the distal portion 208b of the shaft 208 and the treatment assembly 212. For example, as described in further detail below with respect to Figures 3A-3E, an endoscope (not shown) may be positioned to visualize the target site, the positioning of the treatment assembly 212 at the target site, and / or the treatment assembly 212 during therapeutic neuromodulation. In certain embodiments, the distal portion 208b of the shaft 208 is delivered through a working channel extending through the endoscope, thus providing direct, in-line visualization of the target site and the treatment assembly 212. In other embodiments, an endoscope may be incorporated with the treatment assembly 212 and / or the distal portion 208b of the shaft 208 to provide in-line visualization of the assembly 212 and / or surrounding nasal anatomy. In still further embodiments, image guidance may be provided in conjunction with various other guidance modalities, such as image filtering in the infrared (IR) spectrum to visualize the vasculature and / or other anatomical structures, computed tomography (CT), fluoroscopy, ultrasound, optical coherence tomography (OCT), and / or combinations thereof. Additionally, in some embodiments, image guidance components may be integrated with the therapeutic neuromodulation device 202 to provide image guidance during positioning of the treatment assembly 212.

[0055] Once positioned at the target site, therapeutic modulation can be applied to a precise, localized tissue region via the energy delivery element 214 and / or other features of the treatment assembly 212 to induce one or more desired therapeutic neuromodulatory effects, such as disrupting parasympathetic motor and sensory function. The treatment assembly 212 can selectively target postganglionic parasympathetic nerve fibers that innervate the nasal mucosa at a target or treatment site proximal to or at the entrance into the nasal region. For example, the treatment assembly 212 can be positioned to apply therapeutic neuromodulation at least proximal to the SPF (FIG. 1A) to therapeutically modulate nerves that enter the nasal region through the SPF. The treatment assembly 212 can also be positioned below the SPF to apply therapeutic neuromodulation energy across the accessory and microforaminae (e.g., in the palatine bone) through which the smaller medial and lateral branches of the posterior superior lateral nasal nerve enter the nasal region. Targeted energy application at a target site can achieve therapeutic neuromodulation along all or at least a portion of the posterior nasal nerve fibers entering the nasal region. The therapeutic neuromodulation effect is generally, at least in part, a function of power, time, and contact between the energy delivery element and adjacent tissue. For example, in certain embodiments, therapeutic neuromodulation of autonomic nerve fibers is produced by applying RF energy at a power of about 2-20 W (e.g., 5 W, 7 W, 10 W, etc.) for a duration of about 1-20 seconds (e.g., 5-10 seconds, 8-10 seconds, 10-12 seconds, etc.). The therapeutic neuromodulation effect may include partial or complete denervation via thermal ablation and / or non-ablative thermal alteration or injury (e.g., via prolonged heating and / or resistive heating). The desired thermal heating effect may include raising the temperature of the target nerve fibers above a desired threshold to achieve non-ablative thermal alteration or above a higher temperature to achieve ablative thermal alteration. For example, the target temperature may be above body temperature (e.g., approximately 37°C) but below about 90°C (e.g., 70-75°C) for non-ablative thermal alteration, or the target temperature may be about 100°C or higher (e.g., 110°C, 120°C, etc.) for ablative thermal alteration. The desired non-thermal neuromodulatory effect may include altering the electrical signal transmitted within the nerve.

[0056] The hypothermic effect can also provide neuromodulation. As described in more detail below, for example, a cryotherapy applicator may be used to cool tissue at a target site to provide sublethal hypothermia accompanied by therapeutically effective direct cell injury (e.g., necrosis), vascular injury (e.g., starving cells by cutting off nutrients through damage to blood vessels), and subsequent apoptosis. Exposure to cryotherapeutic cooling can cause acute cell death (e.g., immediately after exposure) and / or delayed cell death (e.g., during tissue thawing and subsequent hyperperfusion). Embodiments of the present technology may include cooling a structure positioned at or near the tissue to effectively cool the tissue to a depth where targeted postganglionic parasympathetic nerves reside. For example, the cooling structure is cooled to a degree that causes therapeutically effective cryogenic postnasal neuromodulation.

[0057] In certain embodiments, the system 200 may determine the location of nerves, accessory foramina, and / or microforamina prior to therapy so that therapeutic neuromodulation can be applied to precise regions containing parasympathetic fibers. For example, the system 200 may determine the location of nerves, accessory foramina, and / or microforamina having a length and / or width approximately 3 mm below the SPF. A target site for therapeutic neuromodulation may be identified, and the treatment assembly 212 may apply therapeutic neuromodulation to the identified target site via one or more applications of therapeutic neuromodulation. In other embodiments, the target site may be smaller or larger (e.g., a 3 cm long target area) based on the location of the detected nerve fibers and foramena. This anatomical mapping of nerves allows the system 200 to accurately detect and therapeutically modulate postganglionic parasympathetic fibers that innervate the mucosa at the entry point of many nerves into the nasal cavity. Furthermore, because there are no obvious anatomical markers indicating the location of SPFs, accessory foramina, and microforamina, nerve mapping allows the operator to identify and therapeutically modulate nerves that would otherwise be difficult to identify without complex mucosal dissection. In addition, anatomical mapping may also allow the operator to identify specific structures (e.g., specific arteries) that the operator may wish to avoid during therapeutic neuromodulation.

[0058] Sufficient modulation of at least a portion of the parasympathetic nerves is predicted to slow or potentially block the conduction of autonomic signals to the nasal mucosa, resulting in a long-term or permanent reduction in nasal parasympathetic nerve activity. This is predicted to reduce or eliminate activation or overactivation of submucosal glands and venous congestion, thereby reducing or eliminating the symptoms of rhinosinusitis. Furthermore, because system 200 applies therapeutic neuromodulation to multiple branches of the posterior nasal nerve rather than the single large branch of the posterior nasal nerve that enters the nasal cavity at the SPF, system 200 provides more complete disruption of the parasympathetic pathways that affect the nasal mucosa and lead to rhinosinusitis. Therefore, system 200 is predicted to have an enhanced therapeutic effect for the treatment of rhinosinusitis and reduced reinnervation of the treated mucosa.

[0059] In other embodiments, system 200 may be configured to therapeutically modulate nerves and / or other structures to treat different indications. As described in further detail below, for example, system 200 may be used to determine the location of and / or therapeutically modulate nerves that innervate the paranasal sinuses to treat chronic sinusitis. In further embodiments, system 200 and devices disclosed herein may be configured to therapeutically modulate the vasculature within the nasal anatomy to treat other indications, such as epistaxis (i.e., excessive bleeding from the nose). For example, system 200 and therapeutic neuromodulation devices described herein may be used to apply therapeutically effective energy to arteries (e.g., the sphenopalatine artery and its branches) as they enter the nasal cavity (e.g., via the SPF, accessory foramina, etc.) to partially or completely coagulate or ligate the arteries. In other embodiments, system 200 may be configured to partially or completely coagulate or ligate veins and / or other blood vessels. For such embodiments in which the treatment assembly 212 ligates or coagulates vasculature, the system 200 would be modified to deliver energy at significantly higher powers (e.g., about 100 W) and / or for longer durations (e.g., 1 minute or longer) than would be required for therapeutic neuromodulation. In various embodiments, the system 100 may apply the anatomical mapping techniques disclosed herein to determine the location of or detect the targeted vasculature and surrounding anatomy before, during, and / or after treatment.

[0060] 3A-3E are partial cutaway side views illustrating various approaches for delivering the distal portion of the therapeutic neuromodulation device 202 of FIG. 2 to a target site within the nasal region in accordance with embodiments of the present technology. As shown in FIG. 3A, in various embodiments, the distal portion 208b of the shaft 208 enters the nostril NP, passes through the inferior meatus IM between the inferior turbinate IT and the nasal floor NS, and extends around to the posterior portion of the inferior turbinate IT, where the treatment assembly 212 is deployed at the treatment site. As shown in FIG. 3A, the treatment site may be located proximal to postganglionic parasympathetic access point(s) into the nasal cavity (e.g., the posterior nasal nerve and / or branches of other parasympathetic nerve fibers innervating the nasal mucosa). In other embodiments, the target site may be elsewhere within the nasal cavity, depending on the location of the target nerve. An endoscope 330 and / or other visualization device may be used. , delivered proximal to the target site by extending through the nostril NP and through the middle meatus MM between the inferior turbinate IT and the middle turbinate MT. From a visualization location within the middle meatus MM, the endoscope 330 can be used to visualize the treatment site, the surrounding areas of the nasal anatomy, and the treatment assembly 212.

[0061] As further shown in FIG. 3A , the shaft 208 of the therapeutic neuromodulation device 202 can include a positioning member 332 positioned proximal to the treatment assembly 212 and the target site. In the illustrated embodiment, the positioning member 332 is a balloon that expands within an opening (e.g., one of the nasal passages) against an opposing structure (e.g., between the nasal turbinates) to consistently hold the distal portion 208b of the shaft 208 at a desired location relative to the target site and provide stability for deployment of the treatment assembly 212. In other embodiments, the positioning member 332 may include other expandable structures (e.g., a mesh basket) or fixation features that can be deployed to maintain the shaft 208 in a desired position within the nasal cavity. In further embodiments, the positioning member 332 can be positioned distal to the treatment assembly 212 and expanded within a region distal to the treatment assembly 212 and the treatment site. In still further embodiments, the positioning member 332 is positioned on an introducer sheath (not shown) through which the shaft 208 and / or other devices (e.g., fluid lines for delivery of saline or local anesthetic, endoscopes, sensors, etc.) may pass. The positioning member 332 may be positioned proximal to the target site (e.g., similar to the position shown in FIG. 3A ) or distal to the treatment site. If positioned distally, the introducer sheath may include a side exit port through which the treatment assembly 212 and other features may be deployed at the target site. When the positioning member 332 is positioned on the introducer sheath, the positioning member 332 may provide stability for the delivery and deployment of the distal portion 208b of the shaft 208 and the treatment assembly 212. The positioning member 332 may be incorporated onto the shaft 208, an associated introducer sheath, and / or other delivery features of the system 200 ( FIG. 2 ) when the treatment assembly 212 is delivered through different intraluminal passageways.

[0062] FIG. 3B illustrates a different embodiment in which the distal portion 208b of the shaft 208 enters the nostril NP and passes through the middle meatus MM between the inferior turbinate IT and the middle turbinate, extending posteriorly to deploy the treatment assembly 212 at the treatment site. In this embodiment, the endoscope 330 and / or other visualization device are delivered parallel to the shaft 208 through the same intraluminal pathway as the treatment assembly 212. A pathway through the middle meatus MM may provide a generally straightforward approach to the target site, depending on the particular region of interest and patient anatomical variations. Thus, an approach through the middle meatus MM may require less steering and / or articulation of the shaft 208 and endoscope 330. Furthermore, because the distal portion 208b of the shaft 208 and the endoscope 330 travel along the same delivery path, the endoscope may provide serial or parallel visualization of the treatment assembly 212.

[0063] Similar to the embodiment shown in Figure 3B, Figure 3C illustrates another intraluminal pathway in which the distal portion 208b of the shaft 208 and the endoscope 330 travel side-by-side such that the endoscope 330 may provide serial or parallel visualization of the distal portion 208b of the shaft 208, the treatment assembly 212, and / or the nasal anatomy. However, in the embodiment shown in Figure 3C, the intraluminal pathway extends posteriorly through the inferior meatus IM to the treatment site.

[0064] 3D, in another embodiment, the distal portion 208b of the shaft 208 extends through the middle meatus MM to the treatment site, and the endoscope 330 extends through the inferior meatus IM to a location proximal to the target site. In this embodiment, the endoscope 330 may have an articulating, steerable, or curved distal end that directs the endoscope 330 superiorly to visualize the nasal anatomy and treatment assembly 332 at the target site. For example, the distal end portion of the endoscope 330 may be configured to bend at least 30° to visualize the treatment site. It can be configured as follows.

[0065] As shown in FIG. 3E, in a further embodiment, the distal portion 208b of the shaft 208 can be delivered to the treatment site via the mouth. In this embodiment, therapeutic neuromodulation can be applied to a treatment site in the posterior nasal cavity (e.g., posterior to the SPF). An endoscope 330 (not shown) can enter the nostril NP and extend through the middle meatus MM or inferior meatus IM to a location proximal to the treatment site. Alternatively, the endoscope 330 (not shown) can follow the same path as the shaft 208.

[0066] FIG. 4 is an isometric view of a distal portion of a therapeutic neuromodulation device 402 configured in accordance with an embodiment of the present technology. The therapeutic neuromodulation device 402 may be used in conjunction with the system 200 described above with respect to FIGS. 2-3E. As shown in FIG. 4, the therapeutic neuromodulation device 402 may include a shaft 408 having a proximal portion (not shown) and a distal portion 408b, and a treatment assembly 412 at the distal portion 408b of the shaft 408. The treatment assembly 412 is transformable between a low-profile delivery state to facilitate intraluminal delivery of the treatment assembly 412 to a treatment site within the nasal region and an expanded state (shown in FIG. 4). The treatment assembly 412 includes multiple struts 440 spaced apart from one another to form a frame or basket 442 when the treatment assembly 412 is in the expanded state. The struts 440 may carry one or more energy delivery elements, such as multiple electrodes 444. In the expanded state, the struts 440 may position at least two of the electrodes 444 against tissue at a target site in the nasal region (e.g., proximal to the palate bone below the SPF). The electrodes 444 may apply bipolar or multipolar radio frequency (RF) energy to the target site to therapeutically modulate postganglionic parasympathetic nerves that innervate the nasal mucosa proximal to the target site. In various embodiments, the electrodes 444 may be configured to apply pulsed RF energy with a desired duty cycle (e.g., 1 second on / 0.5 second off) to regulate the temperature increase of the target tissue.

[0067] 4, the basket 442 includes eight branches 446 radially spaced from one another to form at least a generally spherical structure, with each branch 446 including two struts 440 positioned adjacent to one another. However, in other embodiments, the basket 442 may include fewer than eight branches 446 (e.g., 2, 3, 4, 5, 6, or 7 branches) or more than eight branches 446. In further embodiments, each branch 446 of the basket 442 may include a single strut 440, more than two struts 440, and / or the number of struts 440 per branch may vary. In still further embodiments, the branches 446 and struts 440 may form a basket or frame having other suitable shapes for positioning the electrode 444 in contact with tissue at the target site. For example, in the expanded state, the struts 440 may form an oval shape, a hemispherical shape, a cylindrical structure, a pyramidal structure, and / or other suitable shapes.

[0068] As shown in FIG. 4 , the treatment assembly 412 may further include an internal or inner support member 448 extending distally from the distal portion 408 b of the shaft 408. The distal end portion 450 of the support member 448 may support the distal end portion of the strut 440 to form the desired basket shape. For example, as shown in FIG. 4 , the strut 440 may extend distally from the distal portion 408 b of the shaft 408, and the distal end portion of the strut 440 may be attached to the distal end portion 450 of the support member 448. In certain embodiments, the support member 448 may include an internal channel (not shown) through which electrical connectors (e.g., wires) coupled to the electrodes 444 and / or other electrical features of the treatment element 412 may run. In various embodiments, the internal support member 448 may also carry electrodes (not shown) at the distal end portion 450 and / or along the length of the support member 448.

[0069] The basket 442 may be transformed from the low-profile delivery state to the expanded state ( FIG. 4 ) by manipulating a handle (e.g., handle 210 in FIG. 2 ) and / or other features operably coupled to the basket 442 on a proximal portion of the shaft 408. For example, to move the basket 442 from the expanded state to the delivery state, an operator can push the support member 448 distally to bring the struts 440 inward toward the support member 448. An introducer or guide sheath (not shown) may be positioned over the low-profile treatment assembly 412 to facilitate intraluminal delivery or removal of the treatment assembly 412 from or to the target site. In other embodiments, the treatment assembly 412 is transformed between the delivery state and the expanded state using other suitable means.

[0070] The individual struts 440 may be made from a resilient material, such as a shape-memory material (e.g., nitinol), that allows the struts 440 to self-expand into the desired basket 442 shape when in an expanded state. In other embodiments, the struts 440 may be made from other suitable materials, and / or the treatment assembly 412 may be mechanically expanded via a balloon or by proximal movement of the support member 448. The basket 442 and associated struts 440 may be sufficiently rigid to support the electrodes 444 and position or press the electrodes 444 against tissue at the target site. Additionally, the expanded basket 442 may be pressed against surrounding anatomical structures proximal to the target site (e.g., nasal turbinates, palate, etc.), and the individual struts 440 may at least partially conform to the shape of the adjacent anatomical structures to secure the treatment element 412 at the treatment site during energy delivery. Additionally, the expansion and conformability of the struts 440 may facilitate placing the electrodes 444 in contact with the surrounding tissue at the target site.

[0071] At least one electrode 444 is disposed on each strut 440. In the illustrated embodiment, two electrodes 444 are positioned along the length of each strut 440. In other embodiments, the number of electrodes 444 on each strut 440 may be only one, more than two, or zero, and / or the number of electrodes 444 on different struts 440 may vary. The electrodes 444 may be made from platinum, iridium, gold, silver, stainless steel, platinum-iridium, cobalt chromium, iridium oxide, polyethylenedioxythiophene ("PEDOT"), titanium, titanium nitride, carbon, carbon nanotubes, platinum gray, Drawn Filled Tubing ("DFT") with a silver core manufactured by Fort Wayne Metals of Fort Wayne, Indiana, and / or other materials suitable for delivery of RF energy to target tissue.

[0072] In certain embodiments, each electrode 444 can be operated independently of the other electrodes 444. For example, each electrode can be individually activated, and the polarity and amplitude of each electrode can be selected by an operator or a control algorithm (e.g., implemented by the controller 218 of FIG. 2). Various embodiments of such independently controlled electrodes 444 are described in further detail below with reference to FIGS. 5A-5G. Selective, independent control of the electrodes 444 allows the treatment assembly 412 to deliver RF energy to highly customized regions. For example, selected portions of the electrodes 444 can be activated to target nerve fibers within specific regions, while other electrodes 444 remain inactive. In certain embodiments, for example, electrodes 444 can be activated over a portion of the basket 442 adjacent to tissue at a target site, and electrodes 444 not proximal to the target tissue can remain inactive to avoid application of energy to non-target tissue. Such a configuration facilitates selective therapeutic modulation of nerves on the lateral wall of the nose within one nostril without applying energy to structures within other portions of the nasal cavity.

[0073] The electrodes 444 may be electrically coupled to an RF generator (e.g., generator 216 of FIG. 2) via wires (not shown) that extend from the electrodes 444 through the shaft 408 to the RF generator. When each of the electrodes 444 is independently controlled, each electrode 444 may be electrically coupled to an RF generator (e.g., generator 216 of FIG. 2) via wires (not shown) that extend from the electrodes 444 through the shaft 408. In other embodiments, multiple electrodes 444 may be controlled together, such that multiple electrodes 444 may be electrically coupled to the same wire extending through shaft 408. The RF generator and / or components operably coupled thereto (e.g., a control module) may include custom algorithms for controlling activation of electrodes 444. For example, the RF generator may deliver approximately 200-300 W of RF power to the electrodes 444, activating the electrodes 444 in a predetermined pattern selected based on the position of the therapeutic element 412 relative to the identified location of the treatment site and / or target nerve. In other embodiments, the RF generator delivers power at lower levels (e.g., less than 15 W, 15-50 W, 50-150 W, etc.) and / or higher power levels.

[0074] As shown in FIG. 4 , the therapy assembly 412 may further include one or more temperature sensors 452 disposed on the strut 440 and / or other portions of the therapy assembly 412 and configured to detect a temperature adjacent to the temperature sensor 452. The temperature sensor 452 may be electrically coupled to a console (e.g., the console 204 of FIG. 2 ) via wires (not shown) extending through the shaft 408. In various embodiments, the temperature sensor 452 may be positioned proximal to the electrode 444 to detect the temperature at the interface between the tissue and the electrode 444 at the target site. In other embodiments, the temperature sensor 452 may penetrate the tissue at the target site (e.g., a penetrating thermocouple) to detect the temperature at a depth within the tissue. The temperature measurement may provide feedback to the operator or the system regarding the effect of the therapeutic neuromodulation on the tissue. For example, in certain embodiments, an operator may desire to prevent or reduce damage to tissue at a treatment site (e.g., nasal mucosa), and thus temperature sensor 452 may be used to determine whether the temperature of the tissue reaches a predetermined threshold for irreversible tissue damage. Once the threshold is reached, application of therapeutic neuromodulation energy may be terminated so that the tissue may remain intact. In certain embodiments, energy delivery may be automatically terminated based on an evaluation / feedback algorithm (e.g., evaluation / feedback algorithm 220 of FIG. 2 ) stored on a console (e.g., console 204 of FIG. 2 ) operably coupled to temperature sensor 452.

[0075] 5A-5G are isometric views of example electrode configurations of therapeutic neuromodulation devices (individually identified as first through fourth therapeutic neuromodulation devices 502a-502d, respectively, and collectively referred to as therapeutic neuromodulation devices 502) for therapeutic neuromodulation in accordance with embodiments of the present technology. The therapeutic neuromodulation devices 502 of FIGS. 5A-5G may include features generally similar to those of the therapeutic neuromodulation device 402 of FIG. 4. For example, the therapeutic neuromodulation device 502 includes a plurality of struts 440 that form a basket 442 when in an expanded state, and a plurality of electrodes 444 disposed on one or more of the struts 440. In the illustrated embodiment, the first through third therapeutic neuromodulation devices 502a-c shown in Figures 5A-5E include a single strut 440 corresponding to each branch 446 of the basket 442, while the fourth therapeutic neuromodulation device 502d shown in Figures 5F and 5G includes two adjacent struts 440 within each branch 446 of the basket 442. However, in other embodiments, the branches 446 of the therapeutic neuromodulation device 502 may have different amounts of struts 440 and apply RF energy in a manner identical to that described below with reference to Figures 5A-5G. As shown in Figures 5A-5G, the electrodes 444 may be independently controlled and activated via commands from a controller (e.g., controller 218 of Figure 2) or generator (e.g., generator 216 of Figure 2) to apply RF energy over selected regions or segments of the therapeutic assembly 412.

[0076] In the embodiment shown in FIG. 5A, two electrodes 444 of the therapeutic assembly 412 are activated within the first therapeutic neuromodulation device 502a. More specifically, a first electrode 444a on a first strut 440a is activated with a positive polarity, and a second electrode 444b on a second strut 440b, radially spaced from the first strut 440a, is activated with a negative polarity. The remainder of the poles 444 remain inactive. Thus, as indicated by the arrows, current can flow from the first electrode 444a to the second electrode 444b through the target tissue around the circumference or peripheral segment of the treatment assembly 412. This configuration can be used to therapeutically modulate nerves located proximally of the peripheral segment. In other embodiments, different or additional electrodes 444 can be activated with selected polarities to apply therapeutic neuromodulation over selected regions of the treatment assembly 412 in a predetermined manner.

[0077] 5B, the first therapeutic neuromodulation device 502a is configured with three selectively active electrodes 444. A first electrode 444a on the first strut 440a is activated with positive polarity, and second and third electrodes 444b and 444c on the corresponding second and third struts 440b and 440c are activated with negative polarity. The remainder of the electrodes 444 remain inactive. As indicated by the arrows, current flows through tissue from the first electrode 444a to the second and third electrodes 444b and 444c across the segments of the therapeutic assembly 412, thus therapeutically modulating proximally located nerves in the surrounding segments. In the illustrated embodiment, the second and third activated electrodes 444b and 444c are positioned on struts 440b, 440c that are radially spaced from, but adjacent to, the first strut 440a carrying the first active electrode 444a. However, in other embodiments, electrodes 444 are positioned on struts 440b, 440c that are placed further away from the first strut 440a to apply energy over a larger and / or wider segment of the treatment assembly 412.

[0078] In the embodiment shown in FIG. 5C , all of the electrodes 444 in the first hemispherical region 501a of the treatment assembly 412 are activated, and none of the electrodes 444 in the second hemispherical region 501b are activated. The first electrode on the first strut 440a is selectively activated with a positive polarity, and the plurality of electrodes 444 in the first hemispherical region 501a (respectively identified as second through fifth electrodes 444b through 444e) are selectively activated with a negative polarity such that RF energy is applied across the first hemispherical region 501a. This electrode activation configuration can be used to apply RF energy across one side of the basket 442 to therapeutically modulate nerves on the nasal sidewall in one nostril. When the treatment assembly 412 is positioned in the other nostril, a different set of electrodes 444 can be activated across the hemispherical regions of the treatment assembly 412 based on the orientation of the basket 442 relative to the nasal sidewall. Furthermore, because the basket 442 has a generally symmetrical shape (e.g., circular, oval, etc.), and because the electrodes 444 can be selectively activated, the orientation of the basket 442 relative to the target site on the sidewall of the nose does not matter. Instead, the operator can deploy the treatment assembly 412 at the target site without regard to orientation and selectively activate the electrodes 444 in a desired arrangement to apply RF energy across the target site.

[0079] In the embodiment shown in FIG. 5D, the second therapeutic neuromodulation device 502b is configured to selectively control the polarity of the plurality of electrodes 444 across at least a portion of the treatment assembly 412 to apply RF energy in a sesquipolar manner (i.e., bipolar pairing of electrodes, either sequentially or temporarily). In the illustrated embodiment, the first electrode 444a is biased with a positive polarity, and the second through seventh electrodes 444b through 444g are controlled to have a negative polarity. The second through seventh electrodes 444b through 444g are spaced substantially equal distances from the first electrode 444a such that the electrodes 444 are dimensionally pre-arranged to be multiplexed in sequence. During operation, the first through seventh electrodes 444a through 444g are simultaneously activated. However, rather than all of the negative electrodes 444 being simultaneously paired or multiplexed with the positive first electrode 444a, the first electrodes 444a will be paired with each negative electrode 444 in a sequential manner based on the path of least resistance. This path of least resistance is determined by the natural anatomy of the treatment area in contact with the electrode 444. For example, based on the anatomy at the target site, the first electrode 444a may be initially paired with the second electrode 444b. After this initial pairing preference disappears, a second pairing (e.g., with the third electrode 444c) will occur based on the path of least resistance. The first electrode 444a will continue to be sequentially paired in a similar manner with the remaining activated negative electrodes until a threshold is reached and the electrodes 444 reach a state of equilibrium where homogenous current exists between all of the electrode pairs. With each sequential pairing, the treatment assembly 412 increases the size of the ablation zone (i.e., the area to which therapeutic neuromodulation energy is applied). As shown by numbers 1-6 in FIG. 5D, this sequential pairing of electrodes 444 may occur in a circular direction (e.g., counterclockwise or clockwise) based on impedance changes between the electrodes 444. In other embodiments, the sequential pairing of electrodes 444 may occur in different patterns based on the surrounding anatomical context and / or the positioning of the electrodes 444. For example, in the illustrated embodiment, the activated electrodes 444 are positioned within a quadrant of the therapeutic element 412 with equal radial distances between each electrode pair. In other embodiments, the activated electrodes 444 may be positioned over larger or smaller areas of the therapeutic element 412 to apply energy over a larger or smaller treatment area.

[0080] The sesquipolar application of RF energy allows the treatment assembly 412 to intelligently apply RF energy across a target site to therapeutically modulate nerves proximal to the treatment site. For example, when in an equidistant radial relationship to one another, naturally occurring impedance variations between electrode pairs cause the treatment assembly 412 to radially increase the zone of energy application with each pairing. In other embodiments, the electrodes 444 can be configured to be sequentially paired with one another in a manner such that the zone of energy application increases laterally and / or longitudinally based on naturally occurring impedance variations between the electrodes 444. Furthermore, because the sequential impedance-based pairing of the electrodes 444 allows the sesquipolar arrangement of the treatment assembly 412 to inherently limit the energy applied to tissue at the target site, when the impedance at one electrode pairing exceeds a threshold, the next electrode pairing occurs at a lower impedance. In other embodiments, a controller (e.g., controller 218 of FIG. 2) may include instructions (e.g., software) that provide for sequential pairing of electrodes in radial, lateral, longitudinal, and / or spiral fashions.

[0081] In a further embodiment, a portion of the struts 440 themselves may define the electrodes 444. In this embodiment, the struts 440 are made of a conductive material and coated with an insulating material (e.g., a polyxylene polymer, including Paralyene C). A portion of the struts 440 may be left uncoated to define the electrodes 444. The location of the uncoated portions of the struts 440 (i.e., the electrodes 444) may be selected to provide a desired neuromodulation pattern. For example, the uncoated portions may be positioned equally far from the central electrode 444 to allow for sesquipolar RF application. In this embodiment, the conductive struts 440 act as electrical connectors, and thus the treatment assembly 412 does not require as many wires as if the electrodes 444 were separate elements positioned on the struts 440.

[0082] In the embodiment shown in FIG. 5E, the third therapeutic neuromodulation device 502c includes a return electrode 503 at the distal end portion 450 of the support member 448 and selective polarity control of individual electrodes 444 on the struts 440 to provide radial multiplexing of the electrodes 444. The return electrode 503 has a negative polarity and the other electrodes 444 have a positive polarity. In the illustrated embodiment, all of the electrodes 444 are activated, but in other embodiments, the electrodes 444 may be selectively activated based on the desired energy application zone. As indicated by the arrow, this configuration applies RF energy over a distal hemispherical region of the basket 442. In other embodiments, the return electrode 503 is positioned elsewhere on the treatment assembly 412. Thus, electrodes 444, 503 can be used to apply RF energy across different regions of basket 442. In further embodiments, return electrode 503 can be activated along with two or more of electrodes 444 on the strut to apply RF energy in a sesquipolar fashion.

[0083] In the embodiment shown in FIG. 5F, the fourth therapeutic neuromodulation device 502d includes a branch 446 having two adjacent struts 440, with electrodes 444 on the adjacent struts longitudinally spaced from one another and selectively activated to apply energy radially across individual segments. For example, a first electrode 444a on a first strut 440a of a first branch 446a may be selectively activated to have a first polarity, and a second electrode 444b on an adjacent second strut 440b of the first branch 446a may be selectively activated to have a second polarity opposite the first polarity. As indicated by the arrows in FIG. 5F, the first and second electrodes 444a and 444b can then radially apply bipolar RF energy within specific regions of the treatment assembly 412.

[0084] 5F, each strut 440 may include multiple electrodes 444 disposed thereon, and adjacent struts 440 within the same branch 446 may have corresponding amounts of electrodes 444 to allow for bipolar coupling of each of the electrode pairs along distinct regions of the branch 446. In certain embodiments, the electrodes on one strut 440 may all have the same polarity (e.g., coupled to a first wire, not shown), and the electrodes 444 on adjacent struts 440 within the same branch 446 may all have opposite polarities (e.g., coupled to a second wire, not shown). In other embodiments, the electrodes 444 on each strut 440 may be independently controlled to have a desired polarity.

[0085] 5F can be used to detect impedance across a selected region of the treatment assembly 412 defined by the bipolar electrode pairs. The impedance measurement can then be used to identify the presence of nerve fibers within the selected region. If nerves are detected within one or more specific regions associated with an electrode pair, the same electrode pair can be used to apply RF energy to that region and therapeutically modulate the nerves within that region.

[0086] In the embodiment shown in FIG. 5G, the fourth therapeutic neuromodulation device 502d is configured to selectively control the polarity of multiple electrodes 444 across at least a portion of the treatment assembly 412 to apply RF energy in a multipolar manner, in a circular or spiral pattern. As shown in FIG. 5G, the electrodes 444 of one branch 446 can be activated to have a negative polarity, and the electrodes 444 of another branch 446 can be activated to have a positive polarity. The arrangement of the electrodes 444 and the variable distance between the electrodes 444 can vary, such that the energy application zones have different shapes or patterns. In other embodiments, the positive and negative electrodes 444 are spaced apart from one another by a variable distance. Changes in impedance resulting from the surrounding anatomy cause the electrodes to pair with one another in a sequential manner, thereby continually increasing the zone or area to which energy is applied radially and in a generally spiral manner.

[0087] Energy generally propagates deeper into adjacent target tissue the farther the positive and negative electrode pairs are spaced from one another. Thus, the depth of effect of therapeutic neuromodulation energy is expected to increase as linked electrode pairs are positioned farther apart from one another on the basket 442. In the embodiment illustrated in FIG. 5G , for example, electrode pairs in the distal and proximal regions of the basket 442 apply energy to shallower depths within the target tissue than electrode pairs positioned in the central region of the basket 442. Thus, electrode pairs positioned closer together may therapeutically modulate nerves at shallower depths than electrode pairs positioned farther apart from one another. As shown in the illustrated embodiment, some of the electrodes 444 The hives and / or entire branches 446 of the basket 442 may remain inactive to achieve a desired depth of energy application and / or neuromodulation pattern. Selected Embodiments of Neural Detection and Mapping

[0088] Various embodiments of the present technology may include features that measure bioelectric, dielectric, and / or other properties of heterogeneous tissue at a target site within the nasal region to determine the presence, location, and / or activity of nerve fibers, and optionally map the location of detected nerves. The features described below may be incorporated into any of the systems and / or devices disclosed herein to provide an accurate depiction of nerves at the target site.

[0089] Nerve detection can occur (a) prior to application of therapeutic neuromodulation energy to determine the presence or location of nerves at the target site and / or record baseline levels of neural activity, (b) during therapeutic neuromodulation to determine the effect of energy application on nerve fibers at the treatment site, and / or (c) after therapeutic neuromodulation to confirm the effectiveness of treatment on the targeted nerve. Due to anatomical variations in the number and location of parasympathetic nerve fibers innervating the nasal cavity and the multiple access points through which they enter the nasal cavity (e.g., SPFs, accessory foraminasals, and microforaminasal foraminasal foraminasal nerves), such nerve detection and mapping can provide an accurate representation of the neural structure to appropriately treat the parasympathetic nerves, rather than just the one or two major branches of the posterior nasal nerve that traverse the SPF.

[0090] In certain embodiments, the systems disclosed herein may determine anatomical structures, specifically neural structures, at a target site using bioelectrical measurements such as, for example, impedance, resistance, voltage, current density, and / or other parameters (e.g., temperature). The location of the neural structures may then be used to determine which treatment site(s) should involve various anatomical structures for therapeutically effective neuromodulation of the targeted parasympathetic nasal nerve. For example, information may be used to determine treatment site(s) with respect to the location of the nasal turbinates or nasal passages.

[0091] Bioelectrical properties can be detected via electrodes (e.g., electrodes 444 of therapeutic neuromodulation devices 402-502d of FIGS. 4-5G). Electrode pairings on a device (e.g., therapeutic assembly 412 described with respect to FIGS. 4-5G) can be selected to acquire bioelectrical data in specific sections or regions at specific depths of a targeted region. For example, FIGS. 6A and 6B are partial schematic diagrams illustrating electrode 644 configurations for neural sensing configured in accordance with embodiments of the present technology. As shown in FIG. 6A, the further apart the electrodes 644 are from each other, the deeper the current flows into the tissue. Thus, electrodes 644 can be selectively activated based on the depth at which desired measurements are to be made. As shown in FIG. 6B, the spacing between electrodes 644 along a plane (e.g., the surface of the tissue) can affect the region at which measurements are made. Thus, electrodes 644 can be selectively activated to acquire information (e.g., impedance) at a desired depth and over a desired region. In other embodiments, bioelectrical properties may be detected using optical coherence tomography (OCT), ultrasound, and / or other suitable detection modalities.

[0092] Measurement of bioelectrical properties can provide information related not only to the location of nerve fibers but also to the localization of the overall anatomy (e.g., turbinates, nasal passages, bones, etc.), which can be used to facilitate system delivery and localization of target nerves relative to the overall anatomy. For example, global target localization can be determined by evaluating the incident electromagnetic fields on soft and hard tissues within the nasal region, which depends on the local geometry and dielectric properties of those features. For example, due to the layered structure of the anatomy of the nasal cavity (e.g., nasal mucosa, submucosa, periosteum, and bony plate), there are large differences in the relative conductivities of soft and hard tissues, which can be used to distinguish the "deeper" mucosal tissue above the turbinates from the "shallower" tissue outside the turbinates.

[0093] In certain embodiments, measurements for neural mapping can be obtained by applying a constant current to electrodes and measuring the voltage difference between pairs of adjacent electrodes to create a spectral profile or map tissue at a target site. Impedance data can be obtained while applying high, medium, and / or low frequencies to the target tissue. At high frequencies, the current passes directly through cell membranes, and the resulting measurements are indicative of tissue and fluid both outside and inside the cells. At low frequencies, the cell membranes impede the current, providing different defining characteristics of the tissue. Thus, bioimpedance can be used to measure targeted geometric or electrical properties of tissue and / or other structures in the nasal cavity. In addition, complex neural mapping can be performed using frequency-difference reconstruction, which requires measurement data (e.g., impedance) at two different frequencies.

[0094] When detecting nerve location and activity via bioelectrical properties, the spatial orientation, direction, and activity of the detected nerve bundles can be used to further identify and characterize the nerve. For example, the measured bioelectrical properties can distinguish between terminating axons (i.e., entering but not exiting the detection region), branching axons (i.e., increasing in number as they enter and exit the detection region), migrating axons (i.e., entering and exiting the detection region without a change in geometry or number), and / or other properties of the nerve. In addition, the orientation of the axons relative to the electrode array can be determined to indicate whether the nerve fibers extend parallel (X direction), perpendicular (Y direction), penetrating depth (Z direction), and / or at any relative position or angle relative to these parameters. This information can then be used to selectively treat specific nerve fibers. For example, selected electrode configurations can be applied to treat specific regions, and / or the treatment assembly can be moved or manipulated to treat nerves from different orientations or locations.

[0095] In certain embodiments, temperature measurements can be obtained to determine the effects of therapeutic neuromodulation on nasal tissue. For example, FIG. 7 is a graph illustrating threshold levels of nasal tissue electrical conductivity versus temperature. A first curve 701 plots tissue electrical conductivity (σ) in response to temperature, showing that a temperature of approximately 70°C corresponds to a first threshold for irreversible changes in tissue impedance. A second curve 703 shows that tissue electrical conductivity permanently increases significantly (i.e., impedance decreases) after tissue is exposed to a temperature of 70°C, as may occur during therapeutic neuromodulation. If therapeutic neuromodulation is stopped when the tissue temperature is detected to be approximately 70°C, it is expected that there will be a permanently measurable change in tissue conductivity without reaching a stage where the tissue is structurally altered or damaged (e.g., by evaporation, desiccation, etc.). However, if the tissue is exposed to a temperature above a second thermal threshold of approximately 90°C, the tissue will undergo a high degree of tissue desiccation and therefore a significant decrease in electrical conductivity (i.e., a higher level of electrical impedance). A third curve 705 illustrates this lower tissue electrical conductivity after exposure to temperatures above 90° C. Thus, in various embodiments, the systems disclosed herein can be configured to stop neuromodulation when the temperature reaches about 70° C. (e.g., 70-80° C.) to avoid structural changes or damage to the mucosa while still providing what is expected to be therapeutically effective neuromodulation.

[0096] Neurodetection and mapping may provide pre-treatment assessment of neural structure, intra-treatment assessment and feedback on tissue temporal changes during neuromodulation, and / or post-treatment assessment of neural activity as a confirmation of efficacy. In various embodiments, bioelectrical measurements taken pre-, during, and post-treatment may be performed multiple times during each stage of treatment to assess and confirm findings. Pre-treatment assessments may be used to evaluate the bioelectrical properties of the native / host tissue to determine a baseline for subsequent actions and as a reference guide to the original biological signature for identifying anatomical targets of interest (e.g., nerves, microforamina, etc.). This information may be used to place multi-electrode arrays in known spatial configurations and assess electroanatomical properties (e.g., for different tissue types). The location of the target tissue can be determined by detecting and then mapping the impedance (variations in impedance of the target tissue). The resulting anatomical mapping can include configuring multiple (high-density) activation sequences in multiple planes with impedance variations to identify different tissue types and structures. During treatment, impedance measurements can be used to verify that the electrodes maintain good contact with the tissue at the target site. During and after treatment, data can be used to determine whether spectra recorded during or after treatment have a shape consistent with the expected tissue type. After treatment, the information can be used to determine whether the targeted nerve has been therapeutically treated.

[0097] In other embodiments, nerve fiber action potentials can be detected via electrodes and other contacts to dynamically map the location and / or activity of nerves within a target region. For example, recorded action potentials can be used to numerically measure, map, and / or image fast neuronal depolarizations to generate an accurate picture of neural activity. Generally, neuronal membrane depolarization can cause a drop in voltage of approximately 110 μV, last approximately 2 ms, and have an impedance / resistance of 1000 Ω cm to 25 Ω cm. In further embodiments, metabolic recovery processes associated with action potential activity (i.e., to return ionic gradients to normal) can also be detected and used to dynamically map nerves at a target site. Detection of bioelectrical properties associated with these features has the advantage that the changes are much larger (e.g., approximately 1000 times larger) and therefore easier to measure.

[0098] In various embodiments, to enhance the recording of action potentials, non-therapeutic stimulation (e.g., RF energy) can be applied to tissue in the detection region via two or more electrodes of the electrode array. The application of stimulating energy can transiently activate nerve fibers, and the resulting action potentials can be recorded. For example, two or more electrodes of the therapeutic assembly can deliver stimulating pulses of energy, while two or more other electrodes can be configured to detect the resulting action potentials. The stimulating energy pulses are expected to enhance the action potential signal, making it easier to record. Selected Embodiments of Therapeutic Neuromodulation Devices

[0099] 8 and 9 are isometric views of a distal portion of a therapeutic neuromodulation device 802 ("device 802") configured in accordance with an embodiment of the present technology. Device 802 may include various features generally similar to those of therapeutic neuromodulation devices 402 and 502a-d described above with reference to FIGS. 4-5G. For example, device 802 includes a therapeutic assembly 812 at a distal portion 408b of shaft 408. The therapeutic assembly 812 includes a plurality of struts 440 forming branches 446 and defining an expandable frame or basket 442, and one or more electrodes 444 disposed on one or more of the struts 440. As shown in FIGS. 8 and 9, device 902 may further include an expandable member 856 (e.g., a balloon) carried by support member 448 and expandable within basket 442. Expandable member 856 may include a plurality of electrodes 858 disposed on an outer surface of expandable member 856. Electrode 858 may be used for detection of bioelectrical characteristics (e.g., impedance) to enable mapping of neural structures at the target site before, during, and / or after therapeutic neuromodulation via other electrodes 444. In other embodiments, electrode 858 may be configured to apply energy for therapeutic neuromodulation.

[0100] 8 and 9, the electrodes 858 may be positioned on the expandable member 856 in a substantially symmetrical manner and uniform distribution. This provides an expandable array whereby impedance and / or other properties may be detected across the tissue, thus providing a more detailed mapping of the tissue and nerves at the treatment site. In other embodiments, the electrodes 858 may be positioned toward the central portion of the expandable member 856 and / or toward the expandable The electrodes 858 may be grouped around different portions of the flexible member 856. In certain embodiments, the electrodes 858 may be selectively activated with particular polarities, such that the electrode array can be configured in a variety of static configurations and dynamically changed in order (e.g., sesquipolar application of current), which may be advantageous for mapping functions.

[0101] During operation, the expandable member 856 can be inflated or otherwise expanded ( FIG. 9 ) to place at least a portion of the electrode 858 in contact with tissue at the target site. The electrode 858 can measure various bioelectrical properties of the tissue (e.g., impedance, action potential, etc.) to detect, determine the location of, and / or map nerves at the treatment site. In certain embodiments, the electrode 444 on the strut 440 and / or the portion of the electrode 858 on the expandable member 856 can apply stimulatory pulses of RF energy, and the electrode 858 can detect the resulting neural response. After mapping, the expandable member 856 can be contracted or collapsed ( FIG. 8 ), and the electrode 444 on the strut 440 can apply therapeutically effective neuromodulation energy to the target site. For example, the ablation pattern of the electrode 444 can be based on the location of the nerve 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 may themselves be configured to apply neuromodulation energy to the treatment site. After application of neuromodulation energy, the electrodes 858 on the expandable member 856 may again be placed in contact with tissue at the target site and used to record bioelectrical characteristics (e.g., impedance). Detected characteristics (e.g., impedance) obtained before, during, and / or after neuromodulation may be compared to each other to determine whether the neuromodulation was therapeutically effective. If not, the electrodes 444 may again apply therapeutic neuromodulation energy to the same treatment site, or the configuration of the active electrodes 444 may be changed and / or the treatment assembly 812 may be moved to a different treatment site to apply therapeutic neuromodulation energy in a different pattern or sequence.

[0102] FIG. 10A is an isometric view of a distal portion of a therapeutic neuromodulation device 1002 (“device 1002”) configured in accordance with another embodiment of the present technology, and FIG. 10B is an isometric view illustrating the therapeutic neuromodulation device 1002 of FIG. 10A at a treatment site. Device 1002 may include various features generally similar to those of therapeutic neuromodulation devices 402, 502a-d, and 802 described above with reference to FIGS. 4-5G, 8, and 9. For example, device 1002 includes a shaft 1008 and a therapeutic assembly 1012 at a distal portion 1008b of shaft 1008. The therapeutic assembly 1012 includes a plurality of struts 1040 forming branches 1046 and defining an expandable frame or basket 1042, and one or more electrodes 1044 disposed on one or more of the struts 1040. 10A, the device 1002 may further include a secondary or return electrode 1060 disposed along a distal portion of the shaft 1008. In the illustrated embodiment, the return electrode 1060 is a ring electrode having a ring-like shape, although in other embodiments, the return electrode 1060 may have other shapes or configurations.

[0103] The return electrode 1060 may be negatively biased, and at least a portion of the electrodes 1044 on the struts 1040 and / or other portions of the treatment assembly 1012 may be positively biased. As shown by the arrows in Figure 10A, bipolar RF energy may flow over the region extending from the treatment assembly 1012 to the return electrode 1060 on this distal portion 1008b of the shaft 1008. In various embodiments, the RF energy may be applied in a sesquipolar manner (i.e., unbalanced bipolar energy).

[0104] As shown in FIG. 10B, the treatment assembly 1012 is positioned below the SPF and above the inferior turbinate IT and at least a portion of the microforamen MF and nerve N that traverse the palatine bone. A return electrode 1060 may be positioned below the inferior turbinate IT and at least a portion of the microforamina MF and nerve N that traverse the palatine bone. RF energy may then be applied over a broad area extending from the treatment assembly 1012 to the return electrode 1060. As shown in FIG. 10B, for example, the device 1002 may apply energy over the top and bottom of the inferior turbinate, where a high density of microforamina exists.

[0105] 11A-11D are isometric views illustrating a distal portion of a therapeutic neuromodulation device 1102 (individually referred to as a first device 1102a and a second device 1102b) configured in accordance with a further embodiment of the present technology. The first device 1102a may include various features generally similar to those of the therapeutic neuromodulation devices 402, 502a-d, 802, and 1002 described above with reference to FIGS. 4-5G and 8-10B. For example, the first device 1102a includes a shaft 1108 and a therapeutic assembly 1112 at a distal portion 1108b of the shaft 1108. The therapeutic assembly 1112 includes a flexible membrane 1162 carrying a plurality of electrodes 1144 and / or other energy delivery elements arranged in an array across the flexible membrane 1162.

[0106] As shown in FIGS. 11A-11C, the flexible membrane 1162 can be configured to deform from a low-profile delivery state (FIG. 11A) to an expanded state (FIG. 11B) via self-expansion or mechanical expansion means and return to a low-profile delivery or retrieval state (FIG. 11C) for removal of the device from the nasal cavity. In the expanded state shown in FIG. 11B, the flexible membrane can conform to the uneven anatomy of the nasal spaces (e.g., turbinates, sinuses, and / or other paranasal spaces) to enhance the contact area between the flexible membrane 1162 (and electrodes 1144 disposed thereon) and non-planar anatomy. The flexible membrane 1162 can be made from a flexible, dynamic material that supports the electrodes 1144. For example, in certain embodiments, the flexible membrane 1162 can include polymer filaments and / or other materials that add support and structure to the flexible membrane 1162. In various embodiments, the flexible membrane 1162 can have a preset geometry to maintain a predetermined shape. For example, the flexible membrane 1162 and / or the electrode array on the flexible membrane 1162 can maintain a spherical curvature (e.g., as shown in FIG. 11A).

[0107] In various embodiments, the shaft 1108 can be movable relative to the flexible membrane 1162 to enable deployment and recapture of the flexible membrane 1162. For example, the flexible membrane 1162 may be rolled or otherwise folded into a circular shape when in the delivery state ( FIG. 11A ). To move to the expanded state ( FIG. 11B ), components of the shaft 1108 can be rotated and / or moved axially relative to the flexible membrane 1162 to unwind or otherwise expand the flexible membrane 1162 so that it at least partially opens and conforms to the structure of the surrounding anatomy, placing the electrodes 1144 in contact with tissue at the target site. To recapture the device to the retracted state ( FIG. 11C ), the shaft 1108 can again be moved in an axial or rotational manner to roll or otherwise fold the flexible membrane 1162 closely.

[0108] 11A-11C, the electrodes 1144 may be interconnected through multiple connectors 1164, such as, for example, nanoribbons, nanowires, direct inking, multi-directional printing / deposition, and / or other suitable electrical connectors. In various embodiments, the interconnects 1164 between the electrodes 1144 may include periodic wavy conduits or lines having a "U," "S," or elliptical shape. These wavy connectors 1164 may impart a predetermined shape to the flexible membrane 1162, forming multi-dimensional springs within the flexible membrane 1162 and / or promoting apposition of the flexible membrane 1162 against tissue at the target site to improve energy conductivity / transfer.

[0109] The electrodes 1144 are surface mounted on the flexible membrane 1162 or are attached to the flexible membrane 116 The electrodes 1144 may be embedded within a multi-layered composite structure of the two electrodes. In various embodiments, the electrodes 1144 may be relatively small in size, having diameters ranging from 50 to 2,000 microns. The electrodes 1144 may be configured to deliver energy in a unipolar, bipolar, or multipolar manner. For example, multipolar electrodes may be used in bipolar and tetrapolar arrangements to facilitate linear and angled energy connectivity between the electrodes 1144.

[0110] The electrodes 1144 may be connected to connection pads housed within the shaft 1108 and / or to features connected to a proximal portion of the shaft 1108, such as a handle or console. The electrodes 1144 may be connected to the connection pads through conductive connector cables (e.g., metallic cables, polymeric cables, and / or combinations thereof).

[0111] In certain embodiments, the flexible membrane 1162 may also house a feedback system (not shown) for controlling the delivery of RF energy and maintaining predefined treatment parameters. For example, the electronic circuitry of the flexible membrane 1162 may include a thermal sensor that provides temperature feedback to control the energy dissipation and penetration depth of the RF energy. Features of the electronic circuitry of the flexible membrane 1162 may also measure resistance and temperature at the treatment site to determine the effectiveness of therapeutic energy application. This information may be used to adjust energy application and avoid collateral damage to host tissue. For example, energy delivery via the electrode 1144 may be automatically terminated if the detected temperature and / or resistance reaches a predetermined threshold maximum (e.g., a threshold temperature associated with tissue damage). Energy delivery via the electrode 1144 may be automatically or manually adjusted if the detected temperature and / or resistance falls below a predetermined threshold range indicative of parameters associated with therapeutically effective modulation of the parasympathetic nasal nerve. In other embodiments, the feedback system may be incorporated into components communicatively coupled to the electrode 1144 and any additional sensors on the flexible membrane 1162. For example, the feedback system may be stored on console 204 of FIG. 2 and executed by controller 218 (FIG. 2).

[0112] 11D , the second device 1102b may include various features generally similar to those of the first device 1102a described above with reference to FIGS. 11A-11C. For example, the device 1102b of FIG. 11D includes a flexible membrane 1162 carrying a plurality of electrodes 1144 and associated electrical connectors 1164 disposed on or embedded within the flexible membrane 1162. The device 1102b further includes an expandable frame 1166 that supports the flexible membrane 1162. The frame 1166 may have a U-shape and may be made from a shape-memory material (e.g., nitinol). In other embodiments, the frame may have a different shape and / or may be made from a different material suitable for supporting the flexible membrane 1162.

[0113] In operation, the frame 1166 facilitates deployment of the flexible membrane 1162 against the anatomy of the nasal cavity and provides support for the flexible membrane 1162 and the associated array of electrodes 1144. The U-shaped frame 1166 may enhance the ability of the flexible membrane 1162 to contact non-planar anatomy at the target site. In various embodiments, for example, the frame 1166 may function as a cantilever spring to establish positive apposition of the membrane 1162 against the target surface tissue and improve energy conductivity / transfer from the electrodes 1144 to the target tissue.

[0114] 12 is a side view of a distal portion of a therapeutic neuromodulation device 1202 ("device 1202") configured in accordance with a further embodiment of the present technology. Device 1202 includes various features generally similar to those of therapeutic neuromodulation devices 402, 502a-d, 802, 1002, and 1102 described above with reference to FIGS. 4-5G and 8-11. For example, device 1202 includes a treatment assembly 121 including a shaft 1208 and a plurality of energy delivery elements, such as electrodes 1244, at a distal portion 1208b of shaft 1208. 2. In the illustrated embodiment, the treatment assembly 1212 includes four electrodes 1244 arranged along a spiral / helical section 1268 at the distal portion 1208b of the shaft 1208. In other embodiments, however, the treatment assembly 1212 may include one, two, three, or more than four electrodes 1244 and / or may include different energy delivery elements. The treatment assembly 1212 may also include a temperature sensor 1252 (e.g., a thermocouple) and / or other type of sensor to detect various characteristics at the treatment site before, during, and / or after application of therapeutic neuromodulation energy and provide feedback that can be used to control the operation of the treatment assembly 1212. Such sensors may be incorporated into any of the other embodiments of the treatment assembly disclosed herein.

[0115] During delivery of the treatment assembly 1212, the spiral / helical section 1168 of the shaft 1208 can be positioned in a low-profile delivery state in which the section 1268 is substantially narrowed or flattened within the introducer sheath and / or via mechanical components associated with the shaft 1208. At the target site, an operator can transform the spiral / helical section 1268 to an expanded state (shown in FIG. 12 ) to place one or more of the electrodes 1244 in contact with the target tissue. One or more of the electrodes 1244 can then be selectively activated to apply RF energy (e.g., monopolar and / or bipolar RF energy) to tissue at the target site within the nasal region to therapeutically modulate nerves proximal to the treatment site. In other embodiments, the distal section of the shaft 1208 can have other suitable shapes, sizes, and / or configurations that facilitate placement of the electrodes 1244 in contact with tissue at the target site. For example, in further embodiments, the distal portion 1208b of the shaft 1208 may have a semicircular, curved, bent, or straight shape, and / or the treatment assembly 1212 may include multiple support members configured to carry one or more of the electrodes 1244.

[0116] FIG. 13 is a side view of a distal portion of a therapeutic neuromodulation device 1302 (“device 1302”) configured in accordance with yet a further embodiment of the present technology. Device 1302 includes various features generally similar to those of therapeutic neuromodulation devices 402, 502a-d, 802, 1002, 1102, and 1202 described above with reference to FIGS. 4-5G and 8-12. For example, device 1302 includes a shaft 1308 and a treatment assembly 1312 at a distal portion 1308b of shaft 1308 that includes multiple energy delivery elements, such as an array of electrodes 1344. In the embodiment illustrated in FIG. 13, treatment assembly 1312 includes a balloon 1370 that carries electrodes 1344. The support member 1372 extends through the length of the balloon 1370 to support the balloon 1370 and may optionally include a channel through which a guidewire (not shown) may extend to facilitate delivery of the therapeutic assembly 1312 to the target site. In other embodiments, the support member 1372 may be omitted.

[0117] The electrodes 1344 may be made from conductive ink that is printed, sprayed, and / or otherwise disposed on the surface of the balloon 1370. Such conductive ink electrodes facilitate the use of complex electrode configurations. Additionally, thermocouples (not shown) may also be incorporated onto the surface of the balloon 1370 using conductive ink and / or other suitable methods. In other embodiments, the electrodes 1344 may be made from foil and glued to the surface of the balloon 1370. In further embodiments, the electrodes 1344 may be made from other suitable materials that may be disposed on the surface of the balloon 1370 and / or embedded within the material of the balloon 1370.

[0118] Balloon 1370 can be made from a variety of different materials and have a variety of different shapes. For example, as shown in FIG. 13, balloon 1370 has an oval shape when in an expanded state. The balloon 1370 may have a rounded or spherical shape, which is expected to improve conformance to anatomical variations at the target site within the nasal cavity. In other embodiments, the balloon 1370 may have a circular, spherical, irregular, and / or other suitable shape for expansion within the nasal anatomy. The balloon 1370 may be made from a flexible material (e.g., a urethane material) that allows the balloon 1370 to conform to anatomical variations when expanded within the nasal region. In other embodiments, the balloon may be made from a non-compliant material (e.g., polyethylene terephthalate, nylon, etc.) that allows the balloon 1370 to have a defined shape when expanded and promotes attachment of the electrodes 1344 to the balloon surface. In further embodiments, the balloon 1370 may be dip coated to form a spherical tip at the distal end of the shaft 1308.

[0119] Balloon 1370 may be inflated with fluid through openings or ports 1374 in support member 1372 and / or openings in shaft 1308 that are in fluid communication with the interior of balloon 1370. For example, support member 1372 and / or shaft 1308 may include a channel extending along the length of shaft 1308 and connected to a fluid supply at a proximal portion of shaft 1308 so that fluid may be delivered to balloon 1370. Balloon 1370 may be inflated against nasal anatomy at the target site to place electrode 1344 in contact with tissue at the target site.

[0120] At the target site, the electrodes 1344 deliver RF energy to the tissue to therapeutically modulate the nerves at the treatment site. In certain embodiments, an array of electrodes 1344 may be arranged on the balloon 1370 and / or selectively activated to apply transverse bipolar RF energy across a radial region of the balloon 1370 (i.e., extending around a circumferential portion of the balloon 1370). In other embodiments, an array of electrodes 1344 may be arranged on the balloon 1370 and / or selectively activated to apply longitudinal bipolar RF energy across a longitudinal region of the balloon 1370 (i.e., extending between a proximal portion and a distal portion of the balloon 1370).

[0121] In various embodiments, the treatment assembly 1312 may include features that facilitate positioning of the balloon 1370 within the nasal anatomy and proper placement of the electrodes 1344 at the treatment site. For example, as shown in FIG. 13 , an endoscope 1371 may be positioned on the surface of the balloon 1370 to provide direct, in-line visualization of the balloon 1370 and target site during placement at the target site. The treatment assembly 1312 may also include graduated markings 1373 along the surface of the support member 1372 and / or balloon 1370 to indicate the spatial orientation and / or depth positioning of the treatment assembly 1312.

[0122] In certain embodiments, the balloon 1370 may be configured to allow slow perfusion of fluid through the balloon wall to cool the electrode 1344 while energy is applied to the target tissue. For example, such a “perfused” balloon 1370 may include laser drill holes and / or other small openings or holes along at least a portion of the balloon 1370 to allow slow perfusion of fluid (e.g., saline solution) through the balloon wall. As the balloon perfusates the saline solution, the saline solution is expected to improve electrical conductivity between the electrode 1344 and the target tissue, which may enhance the effect of RF energy on nerves at the target site. In other embodiments, cooled fluid may be circulated through the balloon 1470 during activation of the electrode 1444 to cool the electrode 1444 and surrounding tissue during energy delivery.

[0123] 14 is a side view of a distal portion of a therapeutic neuromodulation device 1402 ("device 1402") configured in accordance with an additional embodiment of the present technology. Device 1402 has various features generally similar to those of therapeutic neuromodulation device 1302 described above with reference to FIG. Features include. For example, device 1402 includes a shaft 1408 and a treatment assembly 1412 at a distal portion 1408b of shaft 1408. Treatment assembly 1412 includes a balloon 1470, a support member 1472 that supports balloon 1470, and multiple energy delivery elements, such as an array of electrodes 1444, disposed on balloon 1470. In the embodiment illustrated in FIG. 14, electrodes 1444 are part of a flex circuit 1476 adhered to the surface of balloon 1470. Flex circuit 1476 facilitates the creation of complex electrode arrays that can create highly customizable neuromodulation patterns. In certain embodiments, for example, flex circuit 1476 may include a conductive return electrode along the surface of balloon 1470 and multiple electrodes on the proximal or distal portion of balloon 1470 (e.g., the conical end portion of balloon 1470). Additionally, the flex circuit 1476 may incorporate thermocouples and / or thermistors into the circuitry on the surface of the balloon 1470 to detect the temperature at the treatment site before, during, and / or after energy application.

[0124] 15 is an isometric side view of a distal portion of a therapeutic neuromodulation device 1502 (“device 1502”) configured in accordance with an additional embodiment of the present technology. The device 1502 includes various features generally similar to those of the therapeutic neuromodulation devices 1302 and 1402 described above with reference to FIGS. 13 and 14 . For example, the device 1502 includes a shaft 1508 and a therapeutic assembly 1512 at a distal portion 1508b of the shaft 1508. The therapeutic assembly 1512 includes multiple balloons 1578 positioned about an inner support member 1580 and multiple energy delivery elements, such as electrodes 1544, disposed on one or more of the balloons 1578. In certain embodiments, the balloons 1578 are independently inflatable. This allows for asymmetric and variable inflation of the balloon 1578, thereby enhancing the ability of the treatment assembly 1512 to conform to the uneven geometry of the nasal region at the target site and facilitating apposition of the electrode 1544 to the tissue at the target site.

[0125] In the illustrated embodiment, four independently inflated balloons 1578 are positioned around the circumference of the inner support member 1580. However, in other embodiments, the device 1502 may include fewer than four balloons 1578 or more than four balloons 1578 arranged around the inner support member 1580. In further embodiments, the balloons 1578 may have different sizes and / or shapes and may be positioned along various portions of the inner support member 1580. In still further embodiments, the balloons 1578 are attached to the inner support member 1580 at their end portions and are configured as struts that extend outward from the inner support member 1580 when inflated (e.g., in a manner similar to the struts 440 of the therapeutic neuromodulation device 402 of FIG. 4 ).

[0126] During energy delivery, the electrodes 1544 can be configured to apply bipolar RF energy across electrodes 1544 on different balloons 1578 and / or between electrodes 1544 on the same balloon 1578. In other embodiments, the electrodes 1544 apply energy in a sesquipolar manner. For example, the inner support member 1580 can include a return electrode (not shown), and the electrodes 1544 on two or more of the balloons 1578 can be activated for sesquipolar RF energy delivery.

[0127] 16 is a side cross-sectional view of a distal portion of a therapeutic neuromodulation device 1602 ("device 1602") configured in accordance with an additional embodiment of the present technology. Device 1602 includes various features generally similar to those of the therapeutic neuromodulation devices described above. For example, device 1602 includes a shaft 1608 and a therapeutic assembly 1612 at a distal portion 1608b of shaft 1608. In the embodiment illustrated in FIG. 16, therapeutic assembly 1612 applies cryotherapeutic cooling to therapeutically modulate nerves at a target site. 16 , the cryotherapy assembly 1612 may include an expansion chamber 1682 (e.g., a balloon, an inflatable body, etc.) in fluid communication with one or more supply tubes or lumens 1684 via corresponding openings 1686 in the supply lumen 1684. The supply lumen 1682 may extend along at least a portion of the shaft 1608 and be configured to transport coolant in an at least partially liquid state to the distal portion 1608b of the shaft 1608. An exhaust tube or lumen 1689 (e.g., defined by a portion of the shaft 1608) may be disposed in fluid communication with the inside of the expansion chamber 1682 via an outlet 1688 such that the exhaust lumen 1689 may return the coolant to the proximal portion of the shaft 1608. For example, in one embodiment, a vacuum (not shown) at the proximal portion of the shaft 1608 may be used to exhaust the coolant from the expansion chamber 1682 via the exhaust lumen 1689. In other embodiments, the coolant may be delivered to the proximal portion of the shaft 1608 using other suitable mechanisms known to those skilled in the art.

[0128] During cryotherapy, the openings 1686 in the supply lumen 1684 may restrict the flow of coolant, providing a high pressure differential between the supply lumen 1684 and the expansion chamber 1682, thereby facilitating the expansion of the coolant into a gas phase within the expansion chamber 1682. The pressure drop as the liquid coolant passes through the openings 1682 causes the coolant to expand into a gas, reducing its temperature to a therapeutically effective temperature that may modulate nerve fibers proximal to the treatment site within the nasal cavity. In the illustrated embodiment, the expansion chamber 1682 includes a heat transfer portion 1691 that contacts tissue at the target site and cools it at a rate sufficient to induce cryotherapeutic neuromodulation of postganglionic parasympathetic nerve fibers innervating the nasal mucosa. For example, the treatment assembly 1602 may operate at temperatures below -40°C, -60°C, or -80°C. In other embodiments, the treatment assembly 1602 may operate at higher cryotherapeutic temperatures (e.g., 5°C and -15°C, -20°C, etc.).

[0129] The refrigerant used for cryogenic cooling in device 1602 may be a compressed or condensed gas stored in at least a substantially liquid phase, such as, for example, nitrous oxide (NO), carbon dioxide (CO), a hydrofluorocarbon (e.g., FREON, manufactured and available by EI du Pont de Nemours and Company of Wilmington, DE), and / or other suitable fluid that can be stored at a pressure high enough to be at least substantially liquid at about ambient temperature. For example, R-410A, a non-azeotropic but near-azeotropic mixture of difluoromethane (CHF, also known as HFC-32 or R-32) and pentafluoroethane (CHFCF, also known as HFC-125 or R-125), may be at least substantially liquid at about ambient temperature when contained at a pressure of about 1.45 MPa (210 psi). Under appropriate conditions, these cooling agents can reach cryotherapeutic temperatures at or near their respective normal boiling points (e.g., approximately −88° C. for nitrous oxide) to provide therapeutic neuromodulation.

[0130] In other embodiments, the treatment assembly 1612 may include a cryotherapy applicator rather than the expansion chamber 1682 of Figure 16. Such a cryotherapy applicator may be used for highly targeted treatment of nerves.

[0131] 16, the device 1602 may also include a support member 1690 configured to extend through and support a distal portion of the expansion chamber 1682. The support member 1690 may also include a channel extending along its length and an opening 1692 at a distal end portion of the support member 1690 to facilitate delivery of the treatment assembly 1612 to the treatment site over the guidewire GW.

[0132] 17 is a side cross-sectional view of a distal portion of a therapeutic neuromodulation device 1702 ("device 1702") configured in accordance with an additional embodiment of the present technology. 17 includes various features generally similar to those of the therapeutic neuromodulation devices described in. For example, device 1702 includes a shaft 1708 and a treatment assembly 1712 at a distal portion 1708b of shaft 1708. In the embodiment illustrated in FIG. 17, treatment assembly 1712 is configured to apply direct conductive heating to thermally therapeutically modulate nerves at a target site. As shown in FIG. 17, treatment assembly 1712 may include a balloon 1770 in fluid communication with a supply tube or lumen 1794 (e.g., defined by a portion of shaft 1708) via an outlet at a distal portion of supply lumen 1794. Supply lumen 1794 may extend along at least a portion of shaft 1708 and be insulated to transport a heated fluid (e.g., heated saline) to balloon 1770 at distal portion 1708b of shaft 1708. An exhaust or return tube or lumen 1796 (e.g., defined by a portion of the shaft 1708) may be positioned in fluid communication with the inside of the balloon 1770 via the outlet so that the return lumen 1796 may exhaust fluid to the proximal portion of the shaft 1708 (e.g., using a vacuum at the proximal portion of the shaft 1708).

[0133] During thermal therapeutic neuromodulation, supply lumen 1794 can supply heated fluid to balloon 1770, and exhaust lumen 1796 can be used to exhaust fluid from balloon 1770, causing the heated fluid to circulate through balloon 1770 (e.g., as indicated by the arrows). The heated fluid can be heated to a therapeutically effective temperature that causes time-dependent thermal damage (e.g., as determined using the Arrhenius equation) to target tissue at a treatment site within the nasal cavity and modulates nerve fibers within or proximal to the heated target tissue. In the illustrated embodiment, for example, the wall of balloon 1770 and / or a portion thereof can contact tissue at the target site and heat the tissue at a rate and for a time sufficient to cause thermal damage to the target tissue and provide therapeutic neuromodulation of postganglionic parasympathetic fibers innervating the nasal mucosa.

[0134] 17, the device 1702 may also include a support member 1790 configured to extend through and carry a distal portion of the balloon 1770. The support member 1790 may also include a channel extending along its length and an opening 1792 at a distal end portion of the support member 1790 that may be used to facilitate delivery of the treatment assembly 1712 to the treatment site over the guidewire GW.

[0135] 18 is a side cross-sectional view of a distal portion of a therapeutic neuromodulation device 1802 (“device 1802”) configured in accordance with an additional embodiment of the present technology. The device 1802 includes various features generally similar to those of the therapeutic neuromodulation devices described above. For example, the device 1802 includes a shaft 1808 and a therapeutic assembly 1812 at a distal portion 1808b of the shaft 1808. The therapeutic assembly 1812 may include an inflatable balloon 1870 and a support member 1890 extending through the balloon 1870. The support member 1890 may also include a channel having an opening 1892 to allow guidewire delivery of the therapeutic assembly 1812 to the treatment site.

[0136] Similar to the treatment assembly 1712 of FIG. 17 , the treatment assembly 1812 may apply therapeutically effective heating to tissue at a target site to cause time-dependent thermal tissue damage (e.g., as determined using the Arrhenius equation) and modulate nerve fibers within or near the heated target tissue. However, in the embodiment illustrated in FIG. 18 , heating is provided via a heating element 1898 positioned within the balloon 1880 and carried by the support member 1890 and / or another feature of the treatment assembly 1812. The heating element 1898 may be a plate or other structure that is heated using resistive heating (via a generator) and / or other suitable heating mechanisms. During operation, heat from the heating element 1898 is transferred from the heating element 1898 to the fluid within the balloon 1870, then through the wall of the balloon 1870. The fluid heated by the heating element 1898 can be heated to a therapeutically effective temperature that causes thermal damage to the target tissue at the treatment site within the nasal cavity and modulates nerve fibers within or proximal to the heated target tissue. In certain embodiments, the balloon 1870 can include conductive features (e.g., metallic panels) on its surface to concentrate the heating effect to the targeted area of ​​the balloon 1870.

[0137] In other embodiments, the balloon 1870 may be heated via capacitive coupling to reach a therapeutically effective temperature that causes thermal damage to the target tissue at the treatment site within the nasal cavity and modulates nerve fibers within or near the heated target tissue. For example, the balloon 1870 may be inflated with an isotonic solution, and the balloon 1870 may be ionically agitated at high frequency to allow capacitive energy to be released across the membrane of the balloon 1870 into the target tissue.

[0138] FIG. 19 is a side view of a distal portion of a therapeutic neuromodulation device 1902 (“device 1902”) configured in accordance with an additional embodiment of the present technology. The device 1902 includes various features generally similar to those of the therapeutic neuromodulation devices described above. For example, the device 1902 includes a shaft 1908 and a therapeutic assembly 1912 at a distal portion 1908b of the shaft 1908. In the embodiment illustrated in FIG. 19, the therapeutic assembly 1912 is configured to apply plasma or laser ablation to therapeutically modulate nerves at a target site. As shown in FIG. 19, the therapeutic assembly 1912 may include an ablation element 1999 (e.g., an electrode) on the distal end portion of the shaft 1908. The ablation element 1999 may apply a high-energy laser pulse to ionize molecules within an initial small portion of the pulse. This process introduces a plasma bubble or field (e.g., 100-200 μm) that can be used to desiccate or otherwise destroy tissue and nerves at the target site. The ablation element 1999 can operate at temperatures below 100°C, limiting the thermal effect on surrounding tissue.

[0139] In other embodiments, the ablation element 1999 may perform laser ablation of nerves at the target site. For example, a neural tracer (e.g., indocyanine green (ICG)) may be injected into the target site to stain the nerves at the target site. The ablation element 1999 may be a laser tuned to absorb the spectrum of the neural tracer, thereby ablating the stained nerves at the target site.

[0140] Selected Embodiments of Therapeutic Neuromodulation for the Treatment of Chronic Sinusitis FIG. 20 is a partial cutaway side view illustrating a target site proximal to the ostium of a nasal sinus for a therapeutic neuromodulation device configured in accordance with an embodiment of the present technology. Any of the therapeutic modulation devices and systems described above can be used to therapeutically modulate nerves innervating the sinuses to treat chronic sinusitis and / or similar symptoms. Referring to FIG. 20 , the sinuses include the frontal sinus FS, the sphenoid sinus SS, the maxillary sinus (“MS,” not shown), and the ethmoid sinus or ethmoid cells (not shown), including the posterior ethmoid cells (“PEC”), middle ethmoid cells (“MEC”), and anterior ethmoid cells (“AEC”). Each sinus opens into the nasal cavity at one or more individual ostia. FIG. 20 illustrates the general locations of the ostia of the frontal sinus, sphenoid sinus, maxillary sinus, and the ostia of the posterior, middle, and anterior ethmoid cells.

[0141] Parasympathetic nerves innervate the mucous membranes of the sinuses and stimulate mucus production within the sinuses. Overactivity of the parasympathetic nerves innervating the sinuses can lead to excessive mucus production and congestion of the soft tissues. Inflammation of the soft tissues proximal to the sinuses can cause obstruction of the ducts between the sinuses and the nasal cavity, blocking the ostia to the sinuses. In addition, overactive mucous membranes and / or clogged ostia can cause retention of mucous secretions within the sinuses due to poor drainage from the sinuses. This can lead to infection and ultimately can lead to a state of chronic sinusitis.

[0142] Therapeutic modulation of the parasympathetic nerves, which control sinus autonomic function, is expected to reduce and eliminate overactive mucous secretions and soft tissue congestion, thereby treating chronic sinusitis or related symptoms. Any of the therapeutic neuromodulation devices described above can be used to apply therapeutically effective neuromodulation energy at or proximal to the ostium of the affected sphenoid, maxillary, frontal, and / or ethmoid sinuses to modulate sinus autonomic function. For example, a therapeutic neuromodulation device can be used to apply RF energy, microwave energy, ultrasound energy, cryotherapeutic cooling, therapeutic heating, plasma ablation, and / or laser ablation to treatment sites at or around the sinus ostium. Similar to the devices described above, a therapeutic neuromodulation device can be delivered intracavitarily via the nostrils and through the superior, middle, and / or inferior meatus to access the desired sinus ostium(s). In various embodiments, neural mapping techniques similar to those described above with respect to Figures 6A-9 can be used to localize or detect parasympathetic nerves innervating the ostium before, during, and / or after treatment. Application of therapeutic neuromodulation at a target site proximal to the sinus ostium can disrupt parasympathetic signals to the sinus tissue, leading to the opening of the ostium and its ability to drain fluid. Additional Examples 1. A system for 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 for intraluminal placement at a target site below the sphenopalatine foramen of the human patient; a treatment assembly at the distal portion of the shaft, the treatment assembly comprising an energy delivery element configured to therapeutically modulate postganglionic parasympathetic nerves that innervate the nasal mucosa at the microforamina of the palatine bone of the human patient. 2. The system of Example 1, wherein the energy delivery element is configured to deliver at least one of ultrasound energy, microwave energy, laser energy, or radio frequency (RF) energy to therapeutically modulate the postganglionic parasympathetic nerves. 3. The system of Example 1 or 2, wherein the therapeutic assembly is configured to dispense a drug to chemically modulate the postganglionic parasympathetic nerves. 4. The system of any one of Examples 1-3, wherein the shaft comprises a drug delivery channel having an outlet at the distal portion of the shaft, the drug delivery channel configured to deliver at least one of a local anesthetic or a nerve block to the target site. 5. The system of any one of Examples 1-4, wherein the shaft comprises a fluid channel having an outlet at the distal portion of the shaft, the fluid channel configured to deliver saline to the target site to rinse the treatment area with saline. 6. The system of any one of Examples 1-5, further comprising an introducer having a rigid metal portion, the rigid metal portion sized and shaped to extend through the nasal passage to the target site for delivery of the treatment assembly to the target site. 7. The system of any one of Examples 1-6, wherein the shaft is a steerable catheter shaft and the distal portion of the shaft has a bend radius of 3 mm or less. 8. The system of any one of Examples 1-6, wherein the distal portion of the shaft comprises an articulation region having rigid links sized and shaped to have a bend radius of 3 mm or less. 9. The system of any one of Examples 1-8, further comprising a fixation member along the shaft, the fixation member comprising a balloon configured to expand within a cavity in the nasal region to hold the distal portion of the shaft in an appropriate position for deployment of the treatment assembly at the target site. 10. The system of any one of Examples 1-9, wherein the energy delivery element of the treatment assembly comprises a plurality of electrodes configured to apply RF energy for therapeutically modulating postganglionic parasympathetic nerves. 11. The system of any one of Examples 1-10, wherein the therapeutic assembly comprises a plurality of sensing electrodes configured to detect neural activity at least one of before the therapeutic modulation, during the therapeutic modulation, or after the therapeutic neuromodulation. 12. The therapeutic assembly comprises: a basket deformable between a low-profile delivery state and an expanded state, the basket including a plurality of struts that are radially spaced apart when the basket is in the expanded state; a plurality of electrodes disposed on the struts, the struts 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 1-11, wherein the electrode is configured to apply radio frequency (RF) energy to the target site for therapeutically modulating parasympathetic nerves proximal to the target site. 13. The therapeutic assembly a flexible membrane deformable between a low-profile delivery state and an expanded state; a plurality of electrodes disposed on the flexible membrane; The system of any one of Examples 1-11, wherein the electrode is configured to apply radio frequency (RF) energy to the target site for therapeutically modulating parasympathetic nerves proximal to the target site. 14. The system of example 13, wherein the treatment assembly further comprises a frame supporting the flexible membrane. 15. The distal portion of the shaft is deformable between a low-profile delivery state and an expanded state; the distal portion of the shaft has a spiral / helical shape when the distal portion of the shaft is in the expanded state; the energy delivery element comprises a plurality of electrodes disposed on the distal portion of the shaft and configured to deliver radio frequency (RF) energy to the target site for therapeutically modulating parasympathetic nerves proximal to the target site; The system of any one of Examples 1 to 11, wherein the distal portion of the shaft is configured to position at least one of the electrodes in contact with tissue at the target site when the distal portion of the shaft is in the expanded state. 16. The therapeutic assembly comprises: a balloon that is deformable between a low-profile delivery state and an expanded state; The system of any one of Examples 1 to 11, comprising: a plurality of electrodes disposed on the balloon, the plurality of electrodes configured to deliver radio frequency (RF) energy to the target site for therapeutically modulating parasympathetic nerves proximal to the target site. 17. The system of Example 16, wherein the balloon comprises a plurality of holes configured to allow perfusion of fluid through the balloon when the balloon is in the expanded state. 18. A support extending through the balloon; The system of Example 16, further comprising a plurality of graduated markings on at least one of the support or the balloon for identifying the spatial positioning of the balloon. 19. The therapeutic assembly comprises: a balloon deformable between a low-profile delivery state and an expanded state, the balloon comprising a proximal cone portion; a return electrode on the balloon; The system of any one of Examples 1 to 11, comprising: a flex circuit on the proximal cone portion, wherein the return electrode and the flex circuit are configured to deliver radio frequency (RF) energy to the target site for therapeutically modulating parasympathetic nerves proximal to the target site. 20. The therapeutic assembly comprises: a plurality of independently expandable balloons extending distally from the distal portion of the shaft; The system of any one of Examples 1 to 11, comprising at least one electrode on each of the balloons, the electrode configured to deliver radio frequency (RF) energy to the target site for therapeutically modulating parasympathetic nerves proximal to the target site. 21. The system of Example 20, further comprising an internal support member extending through the area between the balloons and configured to support the balloons, the internal support member including a return electrode. 22. The system of any one of Examples 1-9, wherein the treatment assembly comprises a cryotherapy balloon configured to apply cryogenic cooling to tissue at the target site to therapeutically modulate autonomic activity. 23. The system of any one of Examples 1 to 9, wherein the treatment assembly comprises a balloon sized and shaped to contact tissue in a target state when expanded, and the balloon is configured to circulate a fluid heated to at least 60°C to thermally regulate autonomic nervous activity. 24. The therapeutic assembly comprises: a balloon configured to be expanded with a fluid, the balloon being sized and shaped to contact tissue at the target condition when expanded; The system of any one of Examples 1 to 9, comprising: a heating element within the balloon, the heating element configured to heat the fluid within the balloon to thermally regulate autonomic nervous activity. 25. The system of any one of Examples 1-9, wherein the treatment assembly comprises a plasma ablation probe. 26. A system for 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 intraluminally position the distal portion at a target site, the target site being at least one of proximal to or inferior to a sphenopalatine foramen in a human patient; a treatment assembly at the distal portion of the shaft and deformable between a low-profile delivery state and an expanded state, the treatment assembly comprising a plurality of struts and a plurality of electrodes disposed on the struts, the plurality of struts forming a basket that positions at least two of the electrodes at the target site below the sphenopalatine foramen of the human patient when the treatment assembly is in the expanded state; The system, wherein the electrode is configured to apply radio frequency (RF) energy to the target site for therapeutically modulating parasympathetic nerves proximal to the target site. 27. The plurality of struts comprises at least three struts radially spaced apart from one another in the expanded state to define the basket; 27. The system of example 26, wherein each of the three pillars includes at least one of the electrodes. 28. The basket comprises at least three branches that are radially spaced apart from one another in the expanded state to form the basket; each branch having at least two struts positioned adjacent to one another; 28. The system of example 26 or 27, wherein each strut includes at least one of the electrodes. 29. The system of any one of Examples 26 to 28, further comprising a thermocouple positioned at least proximal to one of the electrodes, the thermocouple configured to detect temperature at the interface between the electrode and tissue adjacent to the electrode when the treatment assembly is in the expanded state. 30. The system of any one of Examples 26-29, wherein each of the electrodes is independently activated and independently assigned to a selective polarity to apply therapeutic neuromodulation over a selected region of the basket. 31. The basket has a spherical or ovoid shape, and the electrodes are selectively activated to The system of any one of Examples 26 to 30, configured to apply RF energy across at least one of a segment, quadrant, or hemisphere of the basket. 32. The plurality of electrodes includes first to third electrodes disposed on corresponding first to third support columns; The system further includes a controller operatively coupled to the plurality of electrodes, the controller having a computer-readable medium having instructions thereon that, when executed by the controller, cause first, second, third, and fourth electrodes of the plurality of electrodes to: the first electrode has a positive polarity; the second and third electrodes have negative polarity; The system of any one of Examples 26-31, wherein the electrodes are activated to apply RF energy in a sesquipolar manner over a selected peripheral region of the basket. 33. The basket includes an internal support member having a distal end portion extending through an area between the plurality of struts and supporting the distal end portions of the plurality of struts; the plurality of struts comprises at least a first strut and a second strut; the plurality of electrodes comprising a first electrode disposed on the first strut, a second electrode disposed on the second strut, and a third electrode disposed on the distal end portion of the inner support member; The system further includes a controller operatively coupled to the plurality of electrodes, the controller having a computer-readable medium having instructions thereon that, when executed by the controller, cause first, second, third, and fourth electrodes of the plurality of electrodes to: the first and second electrodes have positive polarity; the third electrode has a negative polarity; The system of any one of Examples 26-31, wherein the electrodes are activated to apply RF energy across a distal region of the basket. 34. The basket comprises at least two branches that are radially spaced apart from one another when the treatment assembly is in the expanded state; The system of any one of Examples 26 to 31, wherein each branch comprises at least a first pillar and a second pillar positioned adjacent to each other, the first pillar having a first electrode disposed thereon, and the second pillar having a second electrode disposed thereon, the first and second electrodes having opposite polarities and configured to apply RF energy between the first electrode and the second electrode. 35. The basket comprises at least two branches that are radially spaced apart from one another when the treatment assembly is in the expanded state; each branch comprising at least a first strut and a second strut positioned adjacent to one another, the first strut having a first electrode disposed thereon, and the second strut having a second electrode disposed thereon; the first and second electrodes of the first branch are configured to have a positive polarity; The first and second electrodes of the second branch are configured and applied to have a negative polarity; The system of any one of Examples 26-31, wherein the treatment assembly is configured to deliver RF energy between the first branch and the second branch across a peripheral portion of the basket. 36. Further comprising a return electrode disposed on the distal portion of the shaft positioned proximally of the treatment assembly; The system of any one of Examples 26-31, wherein the electrode on the support is configured to have a positive polarity and the return electrode is configured to have a negative polarity. 37. The system of any one of Examples 26-36, wherein at least a portion of the electrodes are configured to detect impedance at the target site to determine the location of a nerve at the target site. 38. The plurality of electrodes on the support pillars is a first plurality of electrodes; the therapeutic assembly comprising: an expandable balloon disposed within the strut; a second plurality of electrodes on the expandable balloon; The system of any one of Examples 26 to 37, wherein when in the expanded state, the expandable balloon positions at least a portion of the second plurality of electrodes in contact with tissue at the target site to detect neural activity at the target site. 39. The system of any one of Examples 26-38, further comprising an RF generator operably connected to the treatment assembly, the RF generator including a control device having a computer-readable medium carrying instructions that, when executed by the control device, cause the treatment assembly to detect at least one of impedance or temperature at least proximal to the target site. 40. The system of any one of Examples 26-39, further comprising an RF generator operably connected to the treatment assembly, the RF generator including a control device having a computer-readable medium carrying instructions that, when executed by the control device, cause the treatment assembly to apply RF energy in a predetermined pattern to the target site. 41. A system for neural mapping 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 for intraluminal placement at a target site proximal to the sphenopalatine foramen of the human patient; a plurality of electrodes in the distal portion of the shaft configured to detect the location of the parasympathetic nerves at the target site; a treatment assembly in the distal portion of the shaft, the treatment assembly comprising an energy delivery element configured to therapeutically modulate postganglionic parasympathetic nerves that innervate the nasal mucosa at the target site. 42. The system of Example 41, wherein the electrode defines the energy delivery element and is configured to apply radio frequency (RF) energy to the target site. 43. The system of example 41 or 42, wherein the electrode is configured to detect dielectric properties of heterogeneous tissue in the target region to identify the location of parasympathetic nerves. 44. The system of any one of Examples 41 to 43, wherein the electrode is configured to detect impedance characteristics of heterogeneous tissue at the target site to identify the location of parasympathetic nerves. 45. A method of therapeutically modulating nerves in the nasal region of a human patient, comprising: endoluminally advancing a treatment assembly on a distal portion of a shaft of a treatment device to a target site within the nasal region, the target site being proximal to a parasympathetic nerve spanning at least one of a proximal accessory foramen or a microforamen of the sphenopalatine foramen; and applying energy to the target site using the treatment assembly to therapeutically modulate autonomic activity in at least one of the nasal cavity, nasopharynx, or paranasal sinuses. 46. ​​The method of Example 45, wherein advancing the treatment assembly intraluminally to the target site comprises positioning the treatment assembly on the palatine bone of the human patient below the sphenopalatine foramen. 47. The method of Example 45 or 46, wherein advancing the treatment assembly intraluminally to the target site comprises advancing the treatment assembly intraluminally through a nasal entrance of the human patient and through the inferior meatus to the target site. 48. The method of Example 45 or 46, wherein advancing the treatment assembly intraluminally to the target site comprises advancing the treatment assembly intraluminally through a nasal entrance of the human patient and through the middle meatus to the target site. 49. The method of any one of Examples 45-48, further comprising advancing an endoscope intraluminally through the nasal entrance and through the middle meatus of the human patient to visualize the therapeutic assembly at the target site. 50. The method of any one of Examples 45-48, further comprising advancing an endoscope intracavity through the nasal entrance and through the inferior meatus of the human patient to visualize the therapeutic assembly at the target site. 51. Endocavity advancing the treatment assembly to the target site comprises advancing the treatment assembly intracavity through a nasal entrance of the human patient and through the inferior meatus to the target site; The method of Example 45 or 46, wherein the method further comprises advancing an endoscope intracavity through the entrance of the nose of the human patient and through the inferior meatus to visualize the therapeutic assembly at the target site. 52. endoluminally advancing the treatment assembly to the target site comprises endoluminally advancing the treatment assembly through a nasal entrance of the human patient and through a middle nasal meatus to the target site; The method of Example 45 or 46, wherein the method further comprises advancing an endoscope intraluminally through the entrance of the nose of the human patient and through the middle meatus to visualize the therapeutic assembly at the target site. 53. Further comprising advancing an endoscope intraluminally through the nasal entrance of the human patient and through one of the inferior or middle meatus to an area at least proximal to the target site; endoluminally advancing the treatment assembly to the target site; advancing the distal portion of the shaft through a channel of the endoscope and past the target site; The method of example 45 or 46, comprising advancing the treatment assembly out of an opening in the distal portion of the endoscope. 54. The method of Example 45 or 46, wherein intraluminally advancing the treatment assembly to the target site comprises advancing the distal portion of the shaft through the mouth and oropharynx of the human patient to the target site. 55. The method of any one of Examples 45-54, further comprising imaging the target site via infrared (IR) spectroscopy to visualize the vascular system at least proximal to the target site. 56. The method of any one of Examples 45-55, further comprising expanding a fixation member positioned along the distal portion of the shaft within the cavity of the nasal region, the fixation member holding the distal portion of the shaft in a suitable position for deploying the treatment assembly at the target site. 57. The target site is a first target site, and applying energy to the target site comprises applying energy to the first target site, and the method comprises: repositioning the treatment assembly to a second target site within the nasal region; The method of any one of Examples 45-56, further comprising applying energy to the second target site using the therapeutic assembly to therapeutically modulate parasympathetic nerves proximal to the second target site. 58. The method of any one of Examples 45-57, wherein applying energy comprises applying pulsed radio frequency (RF) energy to the target site via multiple electrodes of the thereapeutic element. 59. The method of any one of Examples 45-58, further comprising detecting impedance at the target site to identify the location of parasympathetic nerves extending across at least one of the accessory foramina or microforamina proximal to the sphenopalatine foramen. 60. The method of Example 59, wherein applying energy to the target site comprises applying energy to discrete areas of the treatment assembly corresponding to the location of the parasympathetic nerve identified via impedance measurements. 61. The method of any one of Examples 45-60, wherein the treatment assembly comprises a plurality of electrodes, and applying energy to the target site comprises independently activating each of the electrodes and selecting the polarity of each of the electrodes to apply therapeutic neuromodulation over selective regions of the treatment assembly. 62. The method of Example 61, wherein applying energy to the target site further comprises applying energy within a first hemispherical portion of the treatment assembly, and wherein the treatment assembly does not apply energy to a second hemispherical portion of the treatment assembly. 63. The treatment assembly includes an expandable basket having a plurality of struts with a plurality of electrodes disposed on the struts, and applying energy to the target site is activating a first electrode of the plurality of electrodes to have a positive polarity; Activating at least a second electrode and a third electrode of the plurality of electrodes to have a negative polarity, wherein the first, second, and third electrodes are activated simultaneously, and the second and third electrodes are sequentially paired with the first electrode based on the path of least resistance to continuously apply therapeutic neuromodulation across the region of the basket. 64. The treatment assembly includes an expandable basket having a plurality of struts with a plurality of electrodes disposed on the struts, and applying energy to the target site is activating a first electrode of the plurality of electrodes to have a positive polarity; Activating at least second through sixth electrodes of the plurality of electrodes to have negative polarity, wherein first through sixth electrodes are activated simultaneously and the second through sixth electrodes are sequentially paired with the first electrode based on the path of least resistance to apply therapeutic neuromodulation sequentially across a hemispheric region of the basket. 65. The treatment assembly includes an expandable basket having a plurality of struts with a plurality of electrodes disposed thereon, and an inner support member having a return electrode at a distal end portion of the inner support member, and applying energy to the target site comprises: activating the electrodes on the posts to have a positive polarity; The method of any one of Examples 45 to 62, comprising activating the return electrode to have a negative polarity, the electrode applying RF energy across the distal region of the basket. 66. The treatment assembly comprises an expandable basket having a plurality of branches that are radially spaced apart from one another when the treatment assembly is in an expanded state, each branch comprising at least two adjacent struts with an electrode positioned on each strut; and applying energy to the target site; activating the electrodes on adjacent struts of at least one of the branches such that the electrodes have opposite polarities; Applying RF energy between the electrodes on the adjacent posts. 67. The treatment assembly includes a plurality of electrodes for applying energy to the target site; activating the electrodes of the treatment assembly to have a positive polarity; activating a return electrode disposed on the distal portion of the shaft proximal to the treatment assembly, the return electrode having a negative polarity; The method of any one of Examples 45-62, wherein activating the electrode and the return electrode applies RF energy across the nasal turbinates of the human patient. 68. Detecting neural activity at the target site via a plurality of sensing electrodes prior to applying energy to the target site to therapeutically modulate autonomic neural activity; mapping a location of nerves in the target region based on the detected neural activity; The method of any one of Examples 45-67, wherein applying energy to the target site comprises selectively applying energy to an area based on the location of the detected nerve. 69. The method of example 68, further comprising applying non-therapeutic neural stimulation to the target site prior to detecting neural activity. 70. The method of Example 68, further comprising detecting neural activity via the plurality of sensing electrodes after applying energy to the target site to determine whether the application of energy therapeutically modulated nerves at the target site. 71. The treatment assembly comprises a flexible membrane carrying a plurality of electrodes; Prior to applying energy, the method includes expanding the flexible membrane at the target site to position at least a portion of the electrode in contact with tissue at the target site; The method of any one of Examples 45-62, wherein applying energy to the target site comprises applying RF energy to the target site via the electrode. 72. further comprising transforming the distal portion of the shaft from a low-profile delivery state to an expanded state such that a plurality of electrodes disposed on the distal portion of the shaft are placed in contact with tissue at the target site, the distal portion of the shaft having a spiral / helical shape in the expanded state; The method of any one of Examples 45-62, wherein applying energy at the target site comprises applying RF energy to the target site via the electrode. 73. The treatment assembly comprises a balloon carrying a plurality of electrodes; prior to applying energy, the method further includes expanding the balloon at the target site to position at least a portion of the electrode in contact with tissue at the target site; The method of any one of Examples 45-62, wherein applying energy to the target site comprises applying RF energy to the target site via the electrode. 74. Applying energy to the target site The method of Example 73, further comprising selectively activating the electrodes to apply an electrical current radially across a circumferential segment of the balloon. 75. Applying energy to the target site The method of Example 73, further comprising selectively activating the electrodes to apply an electrical current longitudinally across a longitudinal region of the balloon. 76. The method of Example 73, wherein expanding the balloon includes filling the balloon with a fluid, and the balloon comprises a plurality of holes that allow perfusion of the fluid through the balloon during energy application. 77. The method of Example 73, wherein expanding the balloon includes circulating a fluid through the balloon, the fluid cooling the electrode during energy application. 78. The treatment assembly includes: a plurality of balloons extending distally from the distal portion of the shaft; and prior to applying energy, the method further includes independently expanding the balloon at the target site to position at least a portion of the electrode in contact with tissue at the target site; The method of any one of Examples 45-62, wherein applying energy to the target site comprises applying RF energy to the target site via the electrode. 79. Applying energy to the target site activating a return electrode on an inner support member extending through the plurality of balloons; 79. The method of example 78, further comprising activating at least a portion of the electrodes on the balloon. 80. Measuring tissue temperature at the target site during energy application; 80. The method of any one of examples 45-79, further comprising terminating energy application when a threshold maximum temperature is reached. 81. The method of any one of examples 45-80, further comprising terminating the energy application after a predetermined maximum period of time. 82. Detecting tissue impedance at the target site during energy application; 82. The method of any one of Examples 45-81, further comprising terminating energy application when a threshold impedance value is reached. 83. Detecting tissue impedance at the target site prior to energy application to define a baseline impedance; detecting tissue impedance at the target site during energy application; 83. The method of any one of Examples 45-82, further comprising terminating energy application when a threshold change in impedance from the baseline impedance is reached. 84. The method of any one of Examples 45-57, wherein applying energy to the target site comprises applying therapeutic cryogenic cooling to tissue at the target site to therapeutically modulate autonomic nerve activity within the nasal cavity, the nasopharynx, and / or the paranasal sinuses. 85. Applying energy to the target site The method of any one of Examples 45 to 57, comprising circulating a heated fluid within a balloon such that the outer surface of the balloon contacts tissue at the target site, heating the tissue and thermally modulating autonomic nervous activity at the target site. 86. Applying energy to the target site expanding the balloon so that an outer surface of the balloon contacts tissue at the target site; The method of any one of Examples 45-57, comprising heating a heating element within the balloon, wherein heat from the heating element is transferred to the fluid and to the tissue adjacent to the balloon to thermally regulate autonomic nervous activity. 87. The method of any one of Examples 45-57, wherein applying energy to the target site comprises generating a plasma field to therapeutically modulate nerves at the target site. 88. The method of any one of Examples 45-87, wherein applying energy to the target site therapeutically modulates a cholinergic pathway that signals to the submucosal gland. 89. The method of any one of Examples 45-88, wherein advancing the treatment assembly intraluminally to the target site comprises advancing the treatment assembly intraluminally through accessory foraminas and / or microforaminas in at least one of the superior meatus, middle meatus, inferior meatus, or pterygopalatine fossa to a parasympathetic point of entry into the nasal region. 90. A method of therapeutically modulating nerves in the nasal region, comprising: endoluminally advancing a treatment assembly on a distal portion of a shaft of a treatment device to a target site within the nasal region, the target site being proximal to a parasympathetic nerve proximal to the sphenopalatine foramen; Detecting the location of the parasympathetic nerve at the target site; applying energy to the target site with the treatment assembly based on the detected location of the parasympathetic nerve, wherein applying energy therapeutically modulates autonomic nerve activity in at least one of the nasal cavity, the nasopharynx, or the paranasal sinuses. 91. The method of Example 90, wherein detecting the location of the parasympathetic nerves at the target site includes measuring dielectric properties of heterogeneous tissue within at least one of the nasal cavity, the nasopharynx, and / or the paranasal sinuses on a high-resolution spatial grid. 92. The method of Example 90 or 92, wherein detecting the location of the parasympathetic nerves at the target site comprises measuring dipole properties of heterogeneous tissue within the nasal cavity, the nasopharynx, and / or the paranasal sinuses on a high-resolution spatial grid. 93. The method of any one of Examples 90-92, wherein detecting the location of the parasympathetic nerves at the target site comprises detecting the impedance of heterogeneous tissue in at least one of the nasal cavity, the nasopharynx, or the paranasal sinuses on a high-resolution spatial grid. 94. A device for therapeutic neuromodulation in the nasal region of a human patient, comprising: a delivery catheter having a distal portion configured to position the distal portion at a target site within the nasal region; a flexible support in the distal portion of the delivery catheter; a plurality of electrodes carried by the flexible support; the flexible support is configured to conform to local anatomical irregularities at the target site to provide local compliance and engagement for electrical activation of at least a portion of the electrode; A device wherein the electrode therapeutically modulates parasympathetic nerves in mucosal and submucosal structures in direct or indirect contact with the electrode. 95. The device of Example 94, further comprising a controllable recapture mechanism configured to recapture the flexible support after energy delivery to enable withdrawal of the flexible support from the nasal cavity. 96. The device of example 94 or 94, wherein the target site is the sphenopalatine foramen. 97. The device of any one of Examples 94 to 46, wherein the electrodes are configured to be selectively activated to control the direction and associated dissipation of energy for precise and localized energy delivery. 98. A method of therapeutically modulating nerves in the nasal region of a human patient, comprising: endoluminally advancing a treatment assembly on a distal portion of a shaft of a treatment device to a target site within the nasal region, the target site being at least proximal to an ostium of at least one of a frontal sinus, an ethmoid sinus, a sphenoid sinus, or a maxillary sinus of the human patient; and applying energy to the target site using the treatment assembly to therapeutically modulate parasympathetic nerves at the target site to treat chronic sinusitis. 99. Endocavity advancing the treatment assembly to the target site includes positioning the treatment assembly proximal to the ostium of the frontal sinus; 99. The method of claim 98, wherein applying energy to the target site comprises applying energy to at least one of the supraorbital nerve, the supratrochlear nerve, a branch of the supraorbital nerve, a branch of the supratrochlear nerve, or other parasympathetic nerve fibers that innervate the mucosa of the frontal sinus. 100. Endocavity advancing the treatment assembly to the target site includes positioning the treatment assembly proximal to the ostium of the ethmoid sinus; 99. The method of claim 98, wherein applying energy to the target site comprises applying energy to at least one of the anterior ethmoidal branch of the nasociliary nerve, the posterior ethmoidal branch of the nasociliary nerve, the maxillary nerve, a branch of the nasociliary nerve, a branch of the maxillary nerve, or other parasympathetic nerve fibers innervating the mucosa of the ethmoid sinuses. 101. Intraluminally advancing the treatment assembly to the target site includes positioning the treatment assembly proximal to the ostium of the maxillary sinus; 99. The method of claim 98, wherein applying energy to the target site comprises applying energy to at least one of the infraorbital branch of the maxillary nerve, the alveolar branch of the maxillary nerve, or other parasympathetic nerve fibers that innervate the mucosa of the maxillary sinus. 102. Endocavity advancing the treatment assembly to the target site includes positioning the treatment assembly proximal to the ostium of the sphenoid sinus; 99. The method of claim 98, wherein applying energy to the target site comprises applying energy to at least one of the posterior ethmoid branch of the optic nerve, the maxillary nerve, a branch of the optic nerve, a branch of the maxillary nerve, or other parasympathetic nerve fibers innervating the mucosa of the sphenoid sinus. 103. A system for therapeutic neuromodulation in the nasal region of a human patient for the treatment of chronic sinusitis, comprising: a shaft having a proximal portion and a distal portion, the distal portion configured for intraluminal placement at a target site, the target site being at least proximal to an ostium of at least one of a frontal sinus, an ethmoid sinus, a sphenoid sinus, or a maxillary sinus of the human patient; a treatment assembly in the distal portion of the shaft for treating parasympathetic nerves innervating a mucosa of at least one of the frontal sinus, the ethmoid sinus, the sphenoid sinus, or the maxillary sinus; and a treatment assembly comprising an energy delivery element configured to therapeutically regulate

[0143] conclusion This disclosure is not intended to be exhaustive or to limit the technology to the precise form disclosed herein. While specific embodiments are disclosed herein for illustrative purposes, various equivalent modifications are possible without departing from the technology, as those skilled in the relevant art will recognize. In some cases, well-known structures and functions have not been shown and / or described in detail to avoid unnecessarily obscuring the description of embodiments of the technology. Although method steps may be presented herein in a specific order, in alternative embodiments, the steps may have a different, preferred order. Similarly, certain aspects of the technology disclosed in the context of specific embodiments may be combined or eliminated in other embodiments. Furthermore, while advantages associated with particular embodiments may be disclosed in the context of those embodiments, other embodiments may also exhibit such advantages, and not necessarily all embodiments may exhibit such advantages or other advantages disclosed herein to be within the scope of the technology. Thus, the disclosure and related technology may encompass other embodiments not expressly shown and / or described herein.

[0144] Throughout this disclosure, the singular terms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Similarly, unless the word "or" is expressly limited in reference to a list of two or more items to refer only to a single item to the exclusion of other items, its use in 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. Additionally, terms such as "comprising" are used throughout this disclosure to mean the inclusion of at least the recited feature(s), but not the exclusion, of a greater number of the same feature(s) and / or one or more additional types of feature. Directional terms such as "upper," "lower," "front," "rear," "vertical," and "horizontal" may be used herein to describe and clarify the relationship between various elements. It should be understood that such terms do not indicate absolute orientation. Reference herein to "one embodiment," "an embodiment," or similar phrases means that a particular feature, structure, operation, or characteristic described in connection with that embodiment may be included in at least one embodiment of the technology. Thus, appearances of such a phrase or phrase within the specification 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 providing therapeutic neuromodulation in the nasal region of a human patient to treat a condition, the system comprising: a treatment device comprising: an end effector configured to deliver energy to tissue at one or more target sites within a nasal cavity of a human patient and to sense one or more properties of tissue at the one or more target sites, the end effector including a plurality of individual, flexible struts that cooperate to define a deformable frame, the frame being deformable between an expanded state and a low-profile delivery state that facilitates delivery of the end effector to the one or more target sites within a nasal cavity of the human patient; a console unit operatively associated with the treatment device and configured to receive data from the treatment device related to the one or more characteristics of tissue at the one or more target sites, and process the data to provide an operator with information related to the anatomy of the one or more target sites; each of the plurality of individual flexible struts having one or more electrodes; in the expanded state, at least some of the plurality of individual flexible struts are configured to place corresponding electrodes in direct contact with target tissue at the one or more target sites; the target tissue includes postganglionic parasympathetic nerves innervating the nasal mucosa; The electrodes are individually activatable in response to receiving an activation signal from the console unit operatively coupled to the end effector and configured to control energy output from the electrodes.

2. 10. The system of claim 1, wherein the console unit is configured to provide information related to at least one of: identification and location of target and non-target anatomical structures at the one or more target sites before therapeutic neuromodulation; identification and location of target and non-target neural structures at the one or more target sites before therapeutic neuromodulation; real-time feedback related to the effectiveness of therapeutic neuromodulation treatment on one or more target anatomical structures and / or neural structures during therapeutic neuromodulation; and feedback related to the effectiveness of therapeutic neuromodulation treatment on one or more target anatomical structures and / or neural structures after therapeutic neuromodulation.

3. 3. The system of claim 2, wherein the subset of electrodes is configured to deliver non-therapeutic stimulatory energy to tissue at the one or more target sites at frequencies to identify at least one of a target neural structure, a non-target neural structure, a target anatomical structure, and a non-target anatomical structure.

4. 4. The system of claim 3, wherein the subset of electrodes of the end effector is configured to sense at least one characteristic of a target neural structure, a non-target neural structure, a target anatomical structure, and a non-target anatomical structure in response to non-therapeutic stimulatory energy.

5. The system of claim 4 , wherein the characteristic comprises at least one of a physiological characteristic, a bioelectrical characteristic, and a thermal characteristic.

6. 6. The system of claim 5, wherein the bioelectrical property comprises at least one of complex impedance, resistance, reactance, capacitance, inductance, permittivity, conductivity, nerve firing voltage, nerve firing current, depolarization, hyperpolarization, magnetic field, and induced electromotive force.

7. 3. The system of claim 2, wherein the console unit is configured to detect and / or map a location of at least one of a target neural structure, a non-target neural structure, a target anatomical structure, and a non-target anatomical structure, and to control delivery of therapeutic energy from the end effector in a neuromodulation pattern based on the location of at least one of the target neural structure, the non-target neural structure, the target anatomical structure, and the non-target anatomical structure.

8. 10. The system of claim 7, wherein at least some of the electrodes of the end effector are configured to deliver energy based on a neuromodulation pattern at a level sufficient to therapeutically modulate one or more nerves associated with a target nerve and / or target anatomical location, while avoiding non-target nerve and / or target anatomical locations.

9. 3. The system of claim 2, wherein the console unit comprises a controller configured to selectively control energy output from one or more of the electrodes of the end effector, some of the electrodes being independently actuated and controlled, thereby configured to deliver energy independently of one another.

10. 10. The system of claim 9, wherein the controller is configured to adjust energy output from one or more of the electrodes of the end effector based at least in part on real-time feedback related to the effectiveness of therapeutic neuromodulation on one or more target anatomical and / or neural structures during therapeutic neuromodulation.

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