SYSTEMS AND METHODS FOR ASSESSMENT AND REPAIR OF NEURONAL TISSUE
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims benefit of U.S. Provisional Patent Application No. 63/586,859, filed September 29, 2023, the disclosure of which is hereby incorporated by reference in its entirety for all purposes.
TECHNICAL FIELD
[0002] The technology is generally directed to methods and devices involving assessment and treatments of neuronal tissue via a transnasal route.
BACKGROUND
[0003] Olfaction is the sensing of odors. Humans detect odors through the olfactory system within the nose. The human olfactory system can detect thousands, and possibly millions, of odorant molecules, which are perceived to yield a smell. Lining a portion of the nasal cavity is the olfactory epithelium, a thin sheet of mucus-coated neuronal tissue that contains the olfactory receptor cells (i.e. , olfactory neurons), along with supporting cells and basal (stem) cells. Odorant molecules can reach the olfactory epithelium either via the nose, and/or from the mouth. Odorants dissolve into and pass through a layer of mucous overlying the olfactory epithelium and contact the olfactory receptor cells to induce the electrical signaling back to the olfactory bulb and brain allowing for the sensation of smell.
[0004] Olfaction is highly impactful on human wellbeing, social interactions, and quality of life. Loss of smelling function not only affects those important factors, but also can be a sign of dysfunction in higher cognitive ability and processing within the brain. Loss of smell increases odds of mortality greater than three times as compared to normal smelling people, and this demonstrates both the importance of smell to our basic protective mechanisms as well as that smell dysfunction can be a sign of many other metabolic, endocrine, neurodegenerative or other systemic issues. [0005] Chronic rhinosinusitis is a disease state of inflammation or infection involving the paranasal sinuses. The sinuses are lined with a mucosal layer made up of respiratory epithelium. This epithelium contains mucus producing glands as well as cells with tiny cilia (hairs) at their surface, which beat at a particular frequency to keep mucus moving at a normal rate and in the correct direction to clear and filter what is breathed into the nose and produced in the sinuses. Inflammation from multiple causes can lead to swelling of the lining, which in turn can cause mucus blockage which then becomes thickened and stagnant, and when it is not moving correctly, this can become a nidus for bacterial growth and infection.
[0006] Chronic rhinosinusitis is also highly impactful to quality of life and overall productivity, with yearly productivity costs greater than in those with chronic migraine, chronic asthma and diabetes, and health utility values similar to patients suffering from AIDS.
SUMMARY OF THE DISCLOSURE
[0007] Various embodiments are directed towards systems and methods for electrical stimulation to and/or electrical signal recording in various tissues accessible via the nasal cavity. In several embodiments, an endoscopic system comprises an inflatable balloon with one or more electrodes disposed thereon. In many embodiments, the endoscopic system is wireless or cordless. In various embodiments, the inflatable balloon is provided in a tubular shape. In some embodiments, the one or more electrodes are provided as an array. In many embodiments, the one or more electrodes are connected to an amplifier via an insulated track. In several embodiments, the one or more electrodes are utilized in a procedure on a subject in which the inflatable balloon traverses through the nasal cavity to an olfactory epithelium to be treated via electrical stimulation and/or assessed via electrical signal recording.
[0008] In some aspects, the techniques described herein relate to an endoscopic system for providing electrical stimulation or performing electrical recording.
[0009] In some aspects, the techniques described herein relate to an endoscopic system for providing electrical stimulation or performing electrical recording that includes an inflatable balloon including an outer wall, inner wall and inflatable chamber therebetween.
[0010] In some aspects, the techniques described herein relate to an endoscopic system for providing electrical stimulation or performing electrical recording that includes an amplifier system.
[0011] In some aspects, the techniques described herein relate to an endoscopic system for providing electrical stimulation or performing electrical recording that includes one or more electrodes disposed on the outer wall, wherein each electrode is individually in conductive connection with the amplifier system via an insulated track.
[0012] In some aspects, the techniques described herein relate to a system, wherein the inflatable balloon is configured to be cordless after delivery to and positioning within a site of procedure.
[0013] In some aspects, the techniques described herein relate to a system, wherein the inflatable balloon further includes a plurality of apertures that extend from the outer wall to the inner wall and provide a passageway through the inflatable chamber.
[0014] In some aspects, the techniques described herein relate to a system, wherein the inflatable balloon has a tubular shape.
[0015] In some aspects, the techniques described herein relate to a system, wherein the inflatable balloon is composed of material including: polyethylene terephthalate (PET), polytetrafluoroethylene (PTFE), nylon, or urethane.
[0016] In some aspects, the techniques described herein relate to a system, wherein each electrode is individually operable.
[0017] In some aspects, the techniques described herein relate to a system, wherein each electrode is composed of a material including: copper, graphite, titanium, brass, silver, gold, platinum, titanium nitride, indium tin oxide, or an alloy thereof.
[0018] In some aspects, the techniques described herein relate to a system, wherein the one or more electrodes disposed on the outer wall are configured to yield a density gradient electrodes.
[0019] In some aspects, the techniques described herein relate to a system, wherein the density of the one or more electrodes is greater where the outer wall is configured to contact or to come in close proximity with an epithelia having a greater amount of electrical activity as compared to where the outer wall is configured to contact or to come in close proximity with an epithelia having a lesser amount of electrical activity.
[0020] In some aspects, the techniques described herein relate to a system, wherein the amplifier system is disposed on the inner wall of the inflatable balloon.
[0021] In some aspects, the techniques described herein relate to a system, wherein the amplifier system is in wireless connection with a computational processing system; wherein the computational processing system includes one or more applications for performing electrical stimulation or signal recording via the one or more electrodes.
[0022] In some aspects, the techniques described herein relate to a system further including a means for inflating the inflatable balloon.
[0023] In some aspects, the techniques described herein relate to a system further including a connector for connecting the inflatable balloon to the means for inflating the inflatable balloon.
[0024] In some aspects, the techniques described herein relate to a system, wherein the means for inflating the inflatable balloon is integrated with the inflatable balloon.
[0025] In some aspects, the techniques described herein relate to a system, wherein the means for inflating the inflatable balloon is one of: an air pump, a fan, a syringe, or a vacuum system.
[0026] In some aspects, the techniques described herein relate to a system further including a delivery system for delivering the inflatable balloon to a site of procedure.
[0027] In some aspects, the techniques described herein relate to a system, wherein the delivery system can reversibly connect with the inflatable balloon.
[0028] In some aspects, the techniques described herein relate to a system, wherein the delivery system includes a flexible arm for facilitating advancement of the inflatable balloon to the site of procedure.
[0029] In some aspects, the techniques described herein relate to a system, inclusive, wherein the delivery system includes the connector for connecting the inflatable balloon to the means for inflating the inflatable balloon.
[0030] In some aspects, the techniques described herein relate to a system further including a visualization aid to visualize guidance of the inflatable balloon during a procedure. [0031] In some aspects, the techniques described herein relate to a system, wherein the inflatable balloon is configured for electrical stimulation or signal recording of an olfactory epithelium.
[0032] In some aspects, the techniques described herein relate to a system, inclusive, wherein the density of the one or more electrodes is greater where the outer wall is configured to contact or to come in close proximity to an epithelia adjacent to a cribriform plate than where the outer wall is configured to contact or to come in close proximity to an epithelia adjacent to a septum or a middle turbinate.
[0033] In some aspects, the techniques described herein relate to a system, inclusive, wherein the density of the one or more electrodes is greater where the outer wall is configured to contact or to come in close proximity to an epithelia adjacent to a septum than where the outer wall is configured to contact or to come in close proximity to an epithelia adjacent to a middle turbinate.
[0034] In some aspects, the techniques described herein relate to a method of performing electrical stimulation or signal recording from an olfactory epithelium.
[0035] In some aspects, the techniques described herein relate to a method of performing electrical stimulation or signal recording from an olfactory epithelium that includes providing an endoscopic system.
[0036] In some aspects, the techniques described herein relate to a method of performing electrical stimulation or signal recording from an olfactory epithelium, the endoscopic system includes an inflatable balloon including an outer wall, inner wall and inflatable chamber therebetween.
[0037] In some aspects, the techniques described herein relate to a method of performing electrical stimulation or signal recording from an olfactory epithelium, the endoscopic system includes an amplifier system.
[0038] In some aspects, the techniques described herein relate to a method of performing electrical stimulation or signal recording from an olfactory epithelium, the endoscopic system includes one or more electrodes disposed on the outer wall.
[0039] In some aspects, the techniques described herein relate to a method of performing electrical stimulation or signal recording from an olfactory epithelium, each electrode is individually in conductive connection with the amplifier via an insulated track. [0040] In some aspects, the techniques described herein relate to a method of performing electrical stimulation or signal recording from an olfactory epithelium, the endoscopic system includes a means for inflating the inflatable balloon.
[0041] In some aspects, the techniques described herein relate to a method of performing electrical stimulation or signal recording from an olfactory epithelium, the endoscopic system includes a delivery system for delivering the inflatable balloon to a site of stimulation or signal recording.
[0042] In some aspects, the techniques described herein relate to a method of performing electrical stimulation or signal recording from an olfactory epithelium that includes transnasally advancing the inflatable balloon in a deflated state via the delivery system to a site of procedure.
[0043] In some aspects, the techniques described herein relate to a method of performing electrical stimulation or signal recording from an olfactory epithelium that includes inflating the balloon at the site of procedure and positioning one or more of the electrodes to be in proximity to the site of procedure.
[0044] In some aspects, the techniques described herein relate to a method of performing electrical stimulation or signal recording from an olfactory epithelium that includes performing at least one of the following: recording electrical signal from epithelia of the site of procedure using the one or more electrodes or administering electrical stimulation to epithelia of the site of procedure using the one or more electrodes.
[0045] In some aspects, the techniques described herein relate to a method, wherein the inflatable balloon is configured to be cordless after delivery to and positioning within a site of procedure.
[0046] In some aspects, the techniques described herein relate to a method, wherein the inflatable balloon further includes a plurality of apertures that extend from the outer wall to the inner wall and provide a passageway through the inflatable chamber.
[0047] In some aspects, the techniques described herein relate to a method, wherein the amplifier system is in wireless connection with a computational processing system; wherein the computational processing system includes one or more applications for performing electrical stimulation or signal recording via the one or more electrodes. [0048] In some aspects, the techniques described herein relate to a method, wherein the endoscopic system further includes a connector for connecting the inflatable balloon to the means for inflating the inflatable balloon.
[0049] In some aspects, the techniques described herein relate to a method, wherein the means for inflating the inflatable balloon is integrated with the inflatable balloon.
[0050] In some aspects, the techniques described herein relate to a method, wherein the means for inflating the inflatable balloon is one of: an air pump, a fan, a syringe, or a vacuum system.
[0051] In some aspects, the techniques described herein relate to a method, wherein the delivery system can reversibly connect with the inflatable balloon.
[0052] In some aspects, the techniques described herein relate to a method, wherein the delivery system includes a flexible arm for facilitating advancement of the inflatable balloon to the site of procedure.
[0053] In some aspects, the techniques described herein relate to a method, inclusive, wherein the delivery system includes the connector for connecting the inflatable balloon to the means for inflating the inflatable balloon.
[0054] In some aspects, the techniques described herein relate to a method further including visualizing the endoscopic system as the inflatable balloon is advanced to the site of procedure.
[0055] In some aspects, the techniques described herein relate to a method, wherein the site of procedure includes an olfactory epithelium.
[0056] In some aspects, the techniques described herein relate to a method further including: providing an odorant or electrical stimulus to stimulate the olfactory epithelium; and recording electrical signal from the olfactory epithelium using the one or more electrodes.
[0057] In some aspects, the techniques described herein relate to a method, wherein an olfactory system is being assessed for injury or dysfunction.
[0058] In some aspects, the techniques described herein relate to a method further including administering electrical stimulation to an olfactory epithelium using the one or more electrodes. [0059] In some aspects, the techniques described herein relate to a method, wherein the olfactory system is injured or dysfunctional.
BRIEF DESCRIPTION OF THE DRAWINGS
[0060] The description and claims will be more fully understood with reference to the following figures and data graphs, which are presented as exemplary embodiments of the disclosure and should not be construed as a complete recitation of the scope of the various embodiments.
[0061] Figs. 1 to 4 provide an example of a cordless inflatable balloon having a tubular shape and comprising a plurality of electrodes disposed thereon. Fig. 1 provides a perspective view of the inflatable balloon. Fig. 2 provides a view of the exterior wall of the inflatable balloon. Fig. 3 provides a view of the interior wall of the inflatable balloon. Fig. 4 provides a cross-sectional view of an inflatable chamber and aperture of the inflatable balloon.
[0062] Figs. 5 to 7 provide an example of an inflatable balloon having a tubular shape and comprising a plurality of electrodes disposed thereon in contact within the nasal cavity. Fig. 5 provides a sagittal view. Fig. 6 provides a coronal view. Fig. 7 provides a magnified coronal view.
DETAILED DESCRIPTION
[0063] Turning now to the drawings and data, systems and methods for electrical stimulation and/or electrical signal recording from the olfactory system are provided in accordance with the various embodiments of the description. In several embodiments, an endoscopic device delivers electrical stimulation to and/or electrical signal recording from the olfactory system, which is accessible via the nasal cavity. In many embodiments, an endoscopic device provides electrical stimulation to or electrical signal recording from an epithelium (e.g., olfactory epithelium). In several embodiments, the endoscopic device is wireless or cordless when providing electrical stimulation to or recording electrical signal from an epithelium.
[0064] In several embodiments, an endoscopic electrical stimulation or signal recording system comprises an inflatable tubular balloon comprising one or more electrodes for electrical stimulation and/or signal recording. In many embodiments, the one or more electrodes are in conductive connection with an amplifier via an insulated track. In various embodiments, the one or more electrodes can be disposed on the outer surface of the tubular balloon. In many embodiments, the tubular balloon comprises one or more apertures in through the balloon, allowing ambient airflow through the apertures from the inner portion of the tube to the outer portion. When inflated within the nasal cavity, the tubular balloon can expand such that the electrodes on the outer surface are in contact or within close proximity to the epitheliums (and neurons therein). Close proximity is to mean a distance that still allows for electrode transmission and/or recording from the epithelia, which depends on the parameters of electrical transmission and/or recording being utilized during use.
[0065] Many embodiments are directed towards methods of endoscopic electrical stimulation and/or signal recording from via the nasal cavity. In several embodiments, the inflatable tubular balloon comprising one or more electrodes for electrical stimulation and/or signal recording is detachable from a delivery system. Accordingly, in many embodiments, the inflatable tubular balloon is traversed through the nasal cavity via the delivery system to reach an epithelium, where the balloon can be inflated such that it can hold and engage the epitheliums within the cavity. The delivery system can comprise a flexible and steerable arm that can reversibly attach to the balloon, such that the distal end can be flexed and steered around the various structures and turns within the nose and the paranasal sinus system to deliver the balloon to the site of electrical stimulation and/or recordation.
[0066] Over 20 million Americans suffer from some level of olfactory loss. Over 80% of human ability to taste food and drink is dependent on olfaction, thus quality of life and sustained nutrition is greatly affected by loss of smell. Additionally, the olfactory system acts as a harbinger of many neurodegenerative diseases and mental disorders, factors largely in human social interaction and may soon be the basis for drug delivery to the brain to bypass the blood brain barrier. There are over 200 different etiologies for loss of olfaction, including inflammation, infection, trauma or degeneration. Various embodiments are directed towards electrically stimulating the olfactory epithelium and the end receptor neurons (collectively known as the olfactory nerve, or cranial nerve I) to incite or speed regeneration of the olfactory nerve after injury.
[0067] As noted above, chronic rhinosinusitis is also highly impactful to quality of life and overall productivity, with yearly productivity costs greater than in those with chronic migraine, chronic asthma and diabetes, and health utility values similar to patients suffering from AIDS. Various embodiments are directed towards trans-nasally electrically stimulating the nerves and receptor cells within the nasal and sinus lining which send signals to the other respiratory cells to transport mucus and keep the sinus lining healthy and functional, and to incite or speed regeneration of the cilia and respiratory epithelium after injury or inflammation.
[0068] Cranial nerves control our sense of smell, our vision and ability to see clearly, the ability to move our eyes around and move them in the same direction at the same time in order to only see one clear image instead of multiple or double images, our ability to tear and cry and protect the cornea, our ability to move our facial muscles and therefore eat, smile, close and open our eyes and express emotion via facial expression, our ability to hear, and our ability to move our tongues and speak and swallow. Damage to or within these nerves can cause obvious deficits based on their functions outlined above. Various embodiments are directed towards trans-nasally electrically stimulating the cranial nerves and their branches within the sinus and skull base region, to incite or speed regeneration of these nerves if damaged and not functional, or modulate or ablate these nerves if they are overactive or overly sensitized after injury or inflammation.
Endoscopic devices for electrical stimulation or electrical signal recording
[0069] Several embodiments of the disclosure are directed to endoscopic devices for electrical stimulation and/or electrical signal recording. In many embodiments, an endoscopic device comprises one or more electrodes connected to an amplifier via an insulated track to provide electrical current or record electrical signals. In various embodiments, the one or more electrodes is disposed upon an outer surface of an inflatable balloon having a tubular shape. In many embodiments, endoscopic devices comprising one or more electrodes are utilized to provide electrical stimulation to and/or electrical signal recording from various epitheliums via the nasal cavity, including (but not limited to) olfactory epithelium.
[0070] Provided in Figs. 1 to 4 is an example of an endoscopic system 101 for electrical stimulation and/or electrical signal recording. Endoscopic system 101 comprises an inflatable balloon 102 (which as shown, is in the inflated state) having a substantially tubular shape, but can be any shape for providing contact with epithelia within the nasal cavity (e.g., an elongated dome shape). As shown, the endoscopic system comprises an inflatable balloon 102 that comprises an outer wall 103, an inner wall 105, and an inflatable chamber 107 between the outer inner wall. An inner space 106 is formed within the inner wall 105. Although a particular tubular shape is shown, it should be understood that various shapes having an inner space and an outer wall are contemplated (e.g., an elongated dome shape), and the various surfaces of the walls can contour in a variety of ways.
[0071] The balloon of the endoscopic device can connect or be in connection via a connector with an air pump, fan, syringe, and/or vacuum system provide air and/or vacuum to inflate and deflate the balloon. In some implementations, the endoscopic device can disconnect from the connector, air pump, fan, syringe, and/or vacuum system such that the endoscopic device can be inflated within the nasal cavity and the connector can be removed, leaving the remote endoscopic device within the cavity to perform electrical stimulation and/or signal recording. In some embodiments, the endoscopic device comprises an integrated microscale fan or vacuum system that remains with the remote endoscopic device within the cavity when performing electrical stimulation and/or signal recording. In some implementations, outer wall 103 has thickness such that the balloon can conform to a cavity space as it is expanded. A balloon can be composed of any appropriate material, including (but not limited to) polyethylene terephthalate (PET), polytetrafluoroethylene (PTFE), nylon, and urethane.
[0072] Various sizes of balloons can be utilized. In various embodiments, a dilated balloon has diameter between 5 and 40 mm, and a length between 10 and 50 mm. The size of the balloon utilized can vary and can be selected depending on the location of electrical stimulation and/or signal recording. In various embodiments, a dilated balloon has a longest diameter between 5 and 15 mm, between 10 and 20 mm, 15 and 25 mm, between 20 and 30 mm, 25 and 35 mm, or between 30 and 40 mm. In various embodiments, a dilated balloon has a longest length between 10 and 20 mm, 15 and 25 mm, between 20 and 30 mm, 25 and 35 mm, between 30 and 40 mm, 35 and 45 mm, or between 4 and 50 mm.
[0073] Disposed on outer wall 103 of the inflatable balloon are one or more electrodes 109, each having an insulated track 111 that is in connection to an amplifier system 113. Each electrode 109 is exposed such that, when the system is activated, each electrode can provide electrical stimulus to and/or record electrical signals from adjacent epithelia. In some implementations, each electrode is spaced apart from each other electrode such that it can transmit and/or record electrical signals individually from the other electrodes (preventing interference or combination of signals between electrodes). The spacing of electrodes allows for more granular spatial resolution of transmission and/or recording, such that particular electrodes may be individually turned on or off to electrical stimulus and/or receive signals and can provide granular data of the process.
[0074] Each electrode (whether singular or within a plurality) can extend along a track and is in conductive connection with the amplifier system. In several embodiments, each electrode comprises a portion that is embedded in a carrier material to insulate the electrode, which is generally inclusive of the track. Each electrode can comprise an exposed portion to provide electrical stimulation and/or signal recording and is individually operable via the amplifier system. In accordance with many embodiments, an electrode terminal is exposed, but the exposed portion of an electrode does not need to be a terminus. An electrode can be composed of any conductive material and any insulative material can be utilized to cover the insulated portion. Conductive materials that can be utilized as an electrode include (but are not limited to), copper (Cu), graphite, titanium (Ti), brass, silver (Ag), gold (Au), platinum (Pt), titanium nitride (TiN), indium tin oxide (ITO), alloys thereof, and combinations thereof. Materials utilized to insulate electrodes (especially along the tracks) include (but are not limited to) glass, mineral oxides, silicon nitride (SiN), and various polymers. Further, any appropriate diameter of an electrode can be utilized, typically between 5 and 50 pm. In various embodiments, an electrode has a diameter of 5 and 15 pm, 10 and 20 pm, 15 and 25 pm, 20 and 30 pm, 25 and 35 pm, 30 and 40 pm, 35 and 35 pm, or 40 and 50 pm. The diameter size of an electrode can affect its impedance and spatial resolution. Electrodes with larger diameters will have decreased impedance but will also have decreased spatial resolution, as compared to electrodes with smaller diameter. Accordingly, electrode diameter can depend on the amount of stimulation to be provided or signal size to be recorded, and the spatial resolution desired.
[0075] The one or more electrodes can be disposed on the outer surface of the endoscopic device in a variety of configurations. In some implementations, the one or more electrodes are disposed on an outer surface of the inflatable balloon. The one or more electrodes can be provided in any pattern or shape, and the pattern or shape can be regular or irregular. In some implementations, a plurality of electrodes is provided such that the electrodes are evenly spaced along the entirety of the outer wall, such as an evenly patterned array. Alternatively, the plurality of electrodes can be disposed on the outer wall such that the electrodes are more concentrated in some areas and less concentrated or even absent in other areas, such as arrays of clusters. In some configurations, the plurality of electrodes is configured to yield a density gradient, which is to mean a spatial variation of density of the electrodes on the outer surface of the inflatable balloon.
[0076] The endoscopic device can be inserted within the nasal cavity (or another cavity reachable via the transnasal route) for performing electrical stimulation and/or electrical signal recording. Various epithelia within the nasal cavity have higher density of nerves. For example, the olfactory epithelium has various density of nerve endings. The highest density of olfactory nerve endings is near the cribriform plate which is adjacent to the olfactory bulb where the bulk of olfactory nerve bodies reside. Further, the epithelia near the septum has a greater density of nerve endings than the middle turbinate. In some implementations, the outer wall is configured to have some portions that contact and/or come within close proximity to an epithelia (e.g., close proximity when disposed on a surface facing towards an epithelia); other sections will not contact or does not come within close proximity (e.g., close proximity when disposed on a surface facing towards open cavity). In these implementations, electrodes may be disposed in less concentration or may be absent in sections of the outer wall that configured to not contact or come within close proximity to an epithelia (or, vice versa, electrodes may be disposed in greater concentration in sections of the outer wall configured to contact or come in close proximity to an epithelia). In some implementations, the outer wall is configured to have some portions that contact or come within close proximity to epithelia having greater amount of electrical activity (e.g., more neuronal activity); in these implementations, electrodes may be disposed in concentrations to match a relative amount electrical activity of the epithelia. In some implementations of endoscopic devices for providing stimulation to or electrical recording within the nasal cavity, the disposition of electrodes is configured on the outer wall with a higher density in portions that contact or come within proximity of the epithelia adjacent to the cribriform plate as compared to the electrodes that would contact or come within close proximity to epithelia adjacent to the septum and middle turbinate. Further, in some implementations, the disposition of electrodes is configured on the outer wall with a higher density in portions that contact or come within proximity of the epithelia adjacent to the septum as compared to points of contact or in proximity to epithelia adjacent to the middle turbinate. And in some implementations, the disposition of electrodes is configured on the outer wall with a gradient such that portions that contact or come within proximity of the epithelia adjacent to the cribriform plate have a higher density than portions that contact or come within proximity of the epithelia adjacent to the septum; and the portions that contact or come within proximity of the epithelia adjacent to the septum have a higher density than portions that contact or come within proximity of the epithelia adjacent to the middle turbinate.
[0077] Inflatable balloon 102 of the endoscopic system can comprise a plurality of apertures 115, each aperture extending from outer wall 103 to inner wall 105, creating a passageway through inflatable chamber 107. The plurality of apertures 115 allow ambient air to pass through the inflatable balloon, which may be important for conducting various assessments of olfactory activity. In particular, to assess an individual’s ability to respond to odors, odorants can be utilized to provide a particular scent that can stimulate the olfactory nerves and their activity can be assessed utilizing the one or more electrodes 109. Odorants can disperse within the ambient air and travel though inner nasal canal, inner space 106, and the plurality of apertures 115 to reach the olfactory epithelium. These apertures 115 can increase the rate of dispersion of ambient air and odorants for stimulating the olfactory epithelium. The plurality of apertures can be provided in a variety of configurations. In some implementations, the plurality of apertures is provided such that the apertures are evenly spaced along the entirety of the inflatable balloon. But any pattern of apertures can be utilized, which can be regular or irregular. Further, the diameter of the apertures can be any size to allow dispersion of odorants therethrough. With a larger the diameter, odorants can reach the olfactory epithelium with less impedance but is to be balanced with maintaining the integrity of the tubular shape of the inflatable balloon and the positioning of electrodes.
[0078] The endoscopic system 101 can comprise an amplifier system 113 for sending and/or receiving electrical signals to the one or more electrodes 109 via the insulated tracks 111. As depicted in Figs. 3 and 4, amplifier system 113 is disposed on inner wall 105 with insulated tracks 111 traveling along inner wall 105 to and around the edge of the inflatable balloon 102 and along outer wall 103 to the electrodes 109. The amplifier, however, can be disposed anywhere on the inflatable balloon 102 or within inflatable chamber 107 as long as it can be in connection with the one or more electrodes via the insulated tracks. An amplifier can be fairly bulky and thus can impede ambient air flow and thus position of the amplifier can be configured to provide adequate airflow. The epithelia near the middle turbinate has less olfactory nerve endings and thus, in some implementations, the amplifier is configured to be on an inner wall or within the inflatable chamber on a side for contacting or coming in proximity to the epithelia of the middle turbinate.
[0079] The amplifier system can be in wireless connection with a computational processing system. Any wireless system capable of transmitting data can be utilized, such as (for example) Bluetooth, Wi-Fi, cellular data, or any receiver and transmitter connection utilizing radio frequency signals. The computational processing system can communicate with the amplifier to transmit electrical signals to the electrodes, receive electrical signals from the electrodes, and/or collect data and transmit data from the amplifier system back to the computational device. The computational processing system can comprise a processor system, a memory, and one or more applications for performing the electrical stimulation and/or signal recording. The amplifier system can be powered by a battery system, such as (for example) a lithium ion battery system. [0080] The endoscopic system can further comprise a delivery system for delivering the inflatable balloon and the one or more electrodes to the site of electrical stimulation and/or signal recording. The delivery system can comprise a flexible arm that can reversibly connect with the inflatable balloon, which can be utilized to facilitate advancement of the balloon through the nasal cavity to the site of procedure. The flexible arm can be in connection with a handle, which can be utilized for controlling the advancement and/or steering of the flexible arm. The flexible arm can be malleable in a way such that it can flex, bend, kink, and/or curve in any direction. The flexible arm can further comprise a connector that connects the inflatable balloon with an air pump, fan, syringe, and/or vacuum system, when such systems are not integrated within the endoscopic device. The handle can further comprise a means for controlling the inflation and deflation of the balloon. Alternatively, the amplifier system can comprise a means for controlling the inflation and deflation of the balloon by controller the function of the connector and/or an integrated air pump and/or vacuum system. The reversible connection between the inflatable balloon and the flexible arm can be yielded by a threaded screw, a snap-on connector, hook with receiving groove, a flange, a twist lock, a ball and lock pin, or any capable combination of reversible coupling mechanisms.
[0081] In some embodiments, the endoscopic system comprises a visualization aid to help visualize the guidance of the inflatable balloon through the nasal canal and to the site of electrical stimulation and/or signal recording. Radiographic imaging or simple endoscopic visualization can be used to guide the inflatable balloon to the olfactory epithelium.
Methods of use
[0082] Various embodiments are directed towards methods for electrical stimulation and/or signal recording of the nerve endings within a cavity reachable a transnasal route, such as the olfactory epithelium. In some embodiments, electrical stimulation and/or signal recording is done in a procedure setting, where an endoscopic system is transnasally introduced to the olfactory epithelium. In some embodiments, electrical stimulation is utilized to treat an injured or a dysfunctional tissue. In some embodiments, signal recording is utilized to assess the ability of the nerve activity of the olfactory system, which may include providing a stimulus (e.g., release of odorants within ambient air).
[0083] Many embodiments are directed towards assessing an individual for pathologies related to electrical signaling of the olfactory epithelium. Accordingly, an individual can be assessed as follows:
(i) advancing the inflatable balloon with one or more electrodes through the nasal cavity to the olfactory epithelium
(ii) inflating the balloon to expand to the space within the olfactory cleft
(iii) positioning the one or more electrodes in proximity to the tissue to be recorded
(iv) optional: provide a stimulus, such as an odorant or an electrical stimulus
(v) record electrical signals from the olfactory epithelium
[0084] Several embodiments are directed towards treating an individual for olfactory loss. Accordingly, an individual can be treated as follows:
(i) advancing the inflatable balloon with one or more electrodes through the nasal cavity to the olfactory epithelium
(ii) inflating the balloon to expand to the space within the olfactory cleft
(iii) positioning the one or more electrodes in proximity to the tissue to be stimulated
(iv) administer electrical stimulation to olfactory epithelium
(v) optional: repeat administration of electrical stimulation to olfactory epithelium as necessary
[0085] Provided in Figs. 5 to 7 is an example of an endoscopic system within a nasal cavity 501 in contact with the olfactory epithelium. As can be seen in the figures, inflatable balloon 102 has been delivered to the olfactory epithelium and inflated therein. Inflatable balloon 102 has been positioned such that the one or more electrodes 109 on outer wall 103 are in contact with or in proximity to the olfactory epithelium. In particular, the outer wall and electrodes are in contact with the epithelia near the cribriform plate 503, the septum 505, and the middle turbinate and superior turbinate 507. Further, inflatable balloon 102 is positioned such that amplifier system 113 is on the inner wall 105 most near the middle turbinate 507. The plurality of apertures 115 can allow the ambient air and odorants to disperse through the cavity and reach the olfactory epithelium. [0086] Dosing and therapeutic regimens can be administered appropriate to the injury to be treated. In some embodiments, electrical stimulation is administered in a therapeutically effective amount as part of a course of treatment As used in this context, to "treat" means to ameliorate at least one symptom of the disorder to be treated or to provide a beneficial physiological effect. For example, one such amelioration of a symptom could be improvement in olfactory sensation (e.g., identification, discrimination or improved threshold of picking up on odorants upon testing).
[0087] A therapeutically effective amount can be an amount sufficient to prevent reduce, ameliorate or eliminate the symptoms of olfactory loss, other cranial nerve loss, chronic rhinosinusitis, or other ventral skull base pathology. In some embodiments, a therapeutically effective amount is an amount sufficient to increase olfactory sensation and ability.