U.S. patent application number 16/776017 was filed with the patent office on 2020-06-04 for devices, systems, and methods for specializing, monitoring, and/or evaluating therapeutic nasal neuromodulation.
The applicant listed for this patent is National University of Ireland, Galway. Invention is credited to Peter Dockery, Marggie Jones, Ivan Keogh, Ian Stephen O'Brien, Martin O'Halloran, Emily Elizabeth Porter, Brian Shields, David Townley.
Application Number | 20200171302 16/776017 |
Document ID | / |
Family ID | 61163734 |
Filed Date | 2020-06-04 |
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United States Patent
Application |
20200171302 |
Kind Code |
A1 |
Townley; David ; et
al. |
June 4, 2020 |
DEVICES, SYSTEMS, AND METHODS FOR SPECIALIZING, MONITORING, AND/OR
EVALUATING THERAPEUTIC NASAL NEUROMODULATION
Abstract
Devices, systems, and methods for specializing, monitoring,
and/or evaluating therapeutic nasal neuromodulation are disclosed
herein. A targeted neuromodulation system configured in accordance
with embodiments of the present technology can include, for
example, an evaluation/modulation assembly at a distal portion of a
shaft and including a plurality of electrodes. The electrodes are
configured to emit stimulating energy at frequencies for
identifying and locating target neural structures and detect the
resultant bioelectric properties of the tissue. The system can also
include a console that maps locations of the target neural
structures. The evaluation/modulation assembly can then apply
therapeutic neuromodulation energy in a highly tailored
neuromodulation pattern based on the mapped locations of the target
neural structures. Accordingly, the system provides therapeutic
neuromodulation to highly specific target structures while avoiding
non-target structures to reduce collateral effects.
Inventors: |
Townley; David; (County
Clare, IE) ; Shields; Brian; (County Galway, IE)
; Keogh; Ivan; (Galway, IE) ; Dockery; Peter;
(Galway, IE) ; O'Brien; Ian Stephen; (Galway,
IE) ; O'Halloran; Martin; (Galway, IE) ;
Porter; Emily Elizabeth; (Galway, IE) ; Jones;
Marggie; (Galway, IE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
National University of Ireland, Galway |
Galway |
|
IE |
|
|
Family ID: |
61163734 |
Appl. No.: |
16/776017 |
Filed: |
January 29, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
15811449 |
Nov 13, 2017 |
10625073 |
|
|
16776017 |
|
|
|
|
62421135 |
Nov 11, 2016 |
|
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61N 1/0546 20130101;
A61B 2018/00327 20130101; A61B 5/6858 20130101; A61N 1/36075
20130101; A61B 5/0538 20130101; A61N 2007/0021 20130101; A61N
1/36021 20130101; A61B 2018/00434 20130101; A61B 18/1492 20130101;
A61B 2018/00404 20130101; A61B 2018/00577 20130101; A61B 2018/00839
20130101; A61B 2018/0212 20130101; A61B 2018/00267 20130101; A61N
1/3603 20170801; A61N 1/36135 20130101 |
International
Class: |
A61N 1/05 20060101
A61N001/05; A61N 1/36 20060101 A61N001/36; A61B 18/14 20060101
A61B018/14; A61B 5/053 20060101 A61B005/053; A61B 5/00 20060101
A61B005/00 |
Claims
1.-44. (canceled)
45. A treatment system comprising: a treatment device comprising an
end effector comprising a feedback element and a treatment element;
and a console including a controller operably associated with the
treatment device, the controller having a computer-readable medium
carrying instructions, which when executed by the controller,
causes the console to: receive feedback from the feedback element
of the end effector, determine locations of target neural
structures and vessels at a treatment site based on the received
feedback, generate a treatment pattern that distinguishes the
locations of the target neural structures from the locations of the
vessels at the treatment site, and apply treatment via the
treatment element of the end effector to the treatment site
according to the treatment pattern such that treatment is provided
to the target neural structures and not the vessels.
46. The system of claim 45, wherein the feedback from the feedback
element further allows identification of additional anatomical
structures.
47. The system of claim 45, wherein the feedback from the feedback
element further allows confirmation of efficacy of the treatment
and/or enhancement of performance of the system.
48. The system of claim 45, wherein the feedback from the feedback
element further allows for monitoring of neural activity and/or
temperature at the target neural structures during treatment.
49. The system of claim 48, wherein the feedback from the feedback
element further allows for automatically shut off the system when
the neural activity and/or temperature reaches a predetermined
threshold.
50. The system of claim 45, wherein the console comprises a display
and feedback is communicated to a user via the display.
51. The system of claim 50, wherein the display is selected from
the group consisting of: a monitor, a touchscreen, and a user
interface.
52. The system of claim 45, wherein the feedback element comprises
one or more electrodes.
53. The system of claim 52, wherein the one or more electrodes
provide feedback that comprises one or more resistance values for
the target neural structures and the vessels at the treatment
site.
54. The system of claim 53, wherein the resistance feedback is
shown as high resolution spatial grid on a display of the
console.
55. The system of claim 45, wherein the treatment element comprises
a cryotherapy treatment element.
56. The system of claim 45, wherein the treatment element comprises
a delivery state and an expanded state.
57. The system of claim 45, wherein the treatment element is
configured to deliver radiofrequency energy.
58. The system of claim 57, wherein the treatment element comprises
a plurality of electrodes.
59. The system of claim 58, wherein the plurality of electrodes are
arranged on a plurality of struts.
60. The system of claim 45, further comprising a shaft
61. The system of claim 60, further comprising a handle coupled to
the shaft, wherein the handle is configured to allow manipulation
of the shaft.
62. The system of claim 60, wherein the shaft is steerable.
63. The system of claim 62, wherein the shaft comprises a bend
radius.
64. The system of claim 62, wherein the shaft is steerable in at
least two different directions.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims priority to U.S. Provisional
Patent Application No. 62/421,135, filed Nov. 11, 2016, which is
incorporated by reference herein in its entirety.
TECHNICAL FIELD
[0002] The present technology relates generally to devices,
systems, and methods for mapping, monitoring, and/or evaluation of
anatomical structures, including neural structures, in or
associated with a nasal region of a patient. In particular, various
embodiments of the present technology are related to devices,
systems, and methods for specializing, monitoring, and/or
evaluating therapeutic nasal neuromodulation.
BACKGROUND
[0003] Rhinosinusitis is characterized as an inflammation of the
mucous membrane of the nose and refers to a group of conditions,
including allergic rhinitis, non-allergic rhinitis, chronic
rhinitis, chronic sinusitis, and medical resistant rhinitis.
Symptoms of rhinosinusitis include nasal blockage, obstruction,
congestion, nasal discharge (e.g., rhinorrhea and/or posterior
nasal drip), facial pain, facial pressure, and/or reduction or loss
of smell. Allergic rhinitis can include further symptoms, such as
sneezing, watery rhinorrhea, nasal itching, and itchy or watery
eyes. Severe rhinitis can lead to exacerbation of coexisting
asthma, sleep disturbances, and impairment of daily activities.
Depending on the duration and type of systems, rhinosinusitis can
fall within four subtypes: acute rhinosinusitis, recurrent
rhinosinusitis, chronic rhinosinusitis with nasal polyposis (i.e.,
soft, non-cancerous growths on the lining of the nasal passages or
sinuses), and chronic rhinosinusitis without nasal polyposis. Acute
rhinosinusitis refers to symptoms lasting for less than twelve
weeks, whereas chronic rhinosinusitis (with and without nasal
polyposis) refers to symptoms lasting longer than twelve weeks.
Recurrent rhinosinusitis refers to four or more episodes of acute
rhinosinusitis within a twelve-month period, with resolution of
symptoms between each episode.
[0004] There are numerous environmental and biological causes of
rhinosinusitis. Non-allergic rhinosinusitis, for example, can be
caused by environmental irritants (e.g., exhaust fumes, cleaning
solutions, latex, perfume, 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 nasal septum deviation. Triggers of
allergic rhinitis can include exposure to seasonal allergens (e.g.,
exposure to environmental allergens at similar times each year),
perennial allergens that occur any time of year (e.g., dust mites,
animal dander, molds, etc.), and/or occupational allergens (e.g.,
certain chemicals, grains, latex, etc.).
[0005] The treatment of rhinosinusitis can include a general
avoidance of rhinitis triggers, nasal irrigation with a saline
solution, and/or drug therapies. Pharmaceutical agents 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 anticholinergic, chromoglycate, and/or anti-immunoglobulin
E therapies. However, these pharmaceutical agents have limited
efficacy (e.g., 17% higher than placebo or less) and undesirable
side effects, such as sedation, irritation, impairment to taste,
sore throat, dry nose, epistaxis (i.e., nose bleeds), and/or
headaches. Immunotherapy, including sublingual immunotherapy
("SLIT"), has also been used to treat allergic rhinitis by
desensitizing the patient to particular allergens by repeated
administration of an allergen extract. However, immunotherapy
requires an elongated administration period (e.g., 3-5 years for
SLIT) and may result in numerous side effects, including pain and
swelling at the site of the injection, urticarial (i.e., hives),
angioedema, asthma, and anaphylaxis.
[0006] Surgical interventions have also been employed in an attempt
to treat patients with drug therapy resistant, severe rhinitis
symptoms. In the 1960's through 1980's, surgeries were performed to
sever parasympathetic nerve fibers in the vidian canal to decrease
parasympathetic tone in the nasal mucosa. More recent attempts at
vidian neurectomies were found to be 50-88% effective for the
treatment of rhinorrhea, with other ancillary benefits including
improvements in symptoms of sneezing and nasal obstruction. These
symptomatic improvements have also been correlated to histologic
mucosal changes with reductions in stromal edema, eosinophilic
cellular infiltration, mast cell levels, and histamine
concentrations in denervated mucosa. However, despite the clinical
and histologic efficacy of vidian neurectomy, resecting the vidian
nerve failed to gain widespread acceptance largely due to the
morbidities associated with its lack of anatomic and autonomic
selectivity. For example, the site of neurectomy includes
preganglionic secretomotor fibers to the lacrimal gland, and
therefore the neurectomy often resulted in the loss of reflex
tearing, i.e., lacrimation, which in severe cases can cause vision
loss. Due to such irreversible complications, this technique was
not more widely adopted. Further, due passage of postganglionic
pterygopalatine fibers through the retro-orbital plexus, the
position of the vidian neurectomy relative to the target end organ
(i.e., the nasal mucosa) may result in re-innervation via the
autonomic plexus and otic ganglion projections traveling with the
accessory meningeal artery, thereby negating the clinical benefits
of the neurectomy.
[0007] The complications associated with vidian neurectomies are
generally attributed to the nonspecific site of autonomic
denervation. Consequently, surgeons have recently shifted the site
of the neurectomy to postganglionic parasympathetic rami that may
have the same physiologic effect as a vidian neurectomy, while
avoiding collateral injury to the lacrimal and sympathetic fibers.
For example, surgeons in Japan have performed transnasal inferior
turbinate submucosal resections in conjunction with resections of
the posterior nasal nerves ("PNN"), which are postganglionic neural
pathways located further downstream than the vidian nerve. (See,
Kobayashi T, Hyodo M, Nakamura K, Komobuchi H, Honda N, Resection
of peripheral branches of the posterior nasal nerve compared to
conventional posterior neurectomy in severe allergic rhinitis.
Auris Nasus Larynx. 2012 Feb. 15; 39:593-596.) The PNN neurectomies
are performed at the sphenopalatine foramen, where the PNN is
thought to enter the nasal region. These neurectomies are highly
complex and laborious because of a lack of good surgical markers
for identifying the desired posterior nasal nerves and, even if the
desired nerves are located, resection of the nerves is very
difficult because the nerves must be separated from the surrounding
vasculature (e.g., the sphenopalatine artery).
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] Many aspects of the present technology can be better
understood with reference to the following drawings. The components
in the drawings are not necessarily to scale. Instead, emphasis is
placed on illustrating clearly the principles of the present
technology. For ease of reference, throughout this disclosure
identical reference numbers may be used to identify identical or at
least generally similar or analogous components or features.
[0009] FIG. 1 is a graph illustrating an action potential of a
nerve.
[0010] FIG. 2A is a graph illustrating neural cell membrane
potential in relation to the opening of various ion channels
opening, and FIG. 2B is a graph illustrating relative neural cell
membrane permeability.
[0011] FIG. 3A is a partially schematic view of a neuromodulation
and mapping system configured in accordance with embodiments of the
present technology.
[0012] FIG. 3B is an enlarged isometric view of a distal portion of
a neuromodulation and mapping device of the neuromodulation and
mapping system of FIG. 3A configured in accordance with embodiments
of the present technology.
[0013] FIGS. 4A-4C are three dimensional views of projected
electrode ablation patterns of a neuromodulation device configured
in accordance with embodiments of the present technology.
[0014] FIG. 5 is an illustration of a projected neuromodulation
zone in relation to anatomical structures in a zone of interest in
accordance with embodiments of the present technology.
[0015] FIG. 6 is an illustration of neural mapping configured in
accordance with embodiments of the present technology.
[0016] FIG. 7 is a block diagram illustrating a method of
anatomical mapping and therapeutic neuromodulation in accordance
with embodiments of the present technology.
[0017] FIGS. 8A and 8B are enlarged isometric views of a distal
portion of a neuromodulation and mapping device configured in
accordance with some embodiments of the present technology.
[0018] FIG. 9 is an enlarged isometric view of a distal portion of
a neuromodulation and mapping device configured in accordance with
some embodiments of the present technology.
DETAILED DESCRIPTION
[0019] The devices, systems, and methods of the present technology
are configured to determine one or more physiological parameters
before, during, and/or after therapeutic nasal neuromodulation for
(1) identifying a treatment location, (2) tailoring the treatment
to a particular patient's anatomy and/or physiology, (3) adjusting
ongoing treatment in real-time, and/or (4) evaluating treatment
efficacy. The targeted neural ablation provided by the systems and
methods described herein are expected to enhance the efficacy of
the neuromodulation therapy and avoid undesired collateral effects.
In several embodiments, the devices, systems, and methods disclosed
herein are configured to measure the
functional/pathophysiological-specific electric, and/or dielectric
properties (i.e., bioelectrical properties or parameters) of
shallow heterogeneous tissue, individual cellular components,
and/or constituents therein on a high resolution spatial grid.
[0020] Specific details of several embodiments of the present
technology are described herein with reference to FIGS. 1-9.
Although many of the embodiments are described with respect to
devices, systems, and methods for mapping, evaluating, and
therapeutically modulating neural structures in the nasal region
for the treatment of rhinitis, other applications and other
embodiments in addition to those described herein are within the
scope of the present technology. For example, at least some
embodiments of the present technology may be useful for neural
mapping and evaluation at other anatomical sites and/or the
treatment of other indications (e.g., chronic sinusitis and
epistaxis). It should be noted that other embodiments in addition
to those disclosed herein are within the scope of the present
technology. Further, embodiments of the present technology can have
different configurations, components, and/or procedures than those
shown or described herein. Moreover, a person of ordinary skill in
the art will understand that embodiments of the present technology
can have configurations, components, and/or procedures in addition
to those shown or described herein and that these and other
embodiments can be without several of the configurations,
components, and/or procedures shown or described herein without
deviating from the present technology. The headings provided herein
are for convenience only and should not be construed as limiting
the subject matter disclosed.
DEFINITIONS
[0021] As used herein, the terms "distal" and "proximal" define a
position or direction with respect to a clinician or a clinician's
control device (e.g., a handle of a neuromodulation catheter). The
terms, "distal" and "distally" refer to a position distant from or
in a direction away from a clinician or a clinician's control
device along the length of device. The terms "proximal" and
"proximally" refer to a position near or in a direction toward a
clinician or a clinician's control device along the length of
device.
[0022] As used herein, "physiological parameters" refer to, at
least in part, one or more of the following: cellular composition,
tissue type, anatomical landscape, bioelectrical properties or
parameters, electric and dielectric measurements, impedance,
resistance, voltage, current density, current frequency, membrane
potential, temperature, pressure, ion concentration,
neurotransmitter concentration, action potential, muscle response
to stimulation, and any derivative (e.g., change in any of the
foregoing, rate of change of any of the foregoing, etc.) and/or
combination of the foregoing and/or as detailed herein.
Bioelectrical properties or parameters refer to any measurable
quantity or quality of a material (e.g., tissue) to describe the
interaction between that material and an electrical or magnetic
source. For example, bioelectrical parameters can include, among
other parameters, resistance, reactance, complex impedance,
capacitance, inductance, permittivity, conductivity, voltage,
current density, current frequency, and/or derivations thereof.
[0023] As used herein, "treatment parameters" refer to one or more
of the following: x, y, and/or z position of the treatment device
and/or electrodes relative to the treated nerves; x, y, and/or z
position of the electrodes relative to one another; shape and/or
layout of the activated electrode array (e.g., ring-shaped,
rectangular, etc.); shape and/or size of electrodes themselves;
number of electrodes; number of treatments (within same procedure
or different procedure); timing and/or activation sequence of
energy delivery from a plurality of electrodes; energy delivery
parameters (discussed below); polarity of electrodes; grouping of
electrodes; and phase angles between voltage sources driving the
electrodes.
[0024] As used herein, "energy delivery parameters" refer to
amplitude, frequency, waveform, phase angle, pulse-repetition
frequency, and pulse width of the applied treatment energy.
[0025] As used herein, "treatment site" refers to an anatomical
location at or proximate to neural structures, such as
parasympathetic fibers, sympathetic fibers, sensory fibers, A-group
nerve fibers, B-group nerve fibers, C-group nerve fibers, and/or
other neural structures, that are eventually targeted for
neuromodulation. It will be appreciated that in certain embodiments
of the present technology, the neural structures that are targeted
for neuromodulation must first be identified and located by the
present technology. Thus, "treatment site" refers to the anatomical
location including or adjacent to the treated neural structures
(e.g., within about 5 mm to about 10 mm, within about 2 mm to about
5 mm, within about 2 mm, etc.). The treatment site can also include
other anatomical structures (e.g., glands) and/or avoid certain
structures (e.g., vessels).
[0026] As used herein, the term "neural structure" refers to the
structures associated with nerves or groups of nerves including,
among other structures, neuronal bundles, axons, dendrites, cell
bodies, parasympathetic fibers, sympathetic fibers, sensory fibers,
A-group nerve fibers, B-group nerve fibers, and/or C-group nerve
fibers.
Relevant Anatomy and Physiology
[0027] The cell bodies, dendrites, and axons of a neuron are
bounded by a cell membrane. The cell membrane includes various
means for pumping sodium ions outwards. This allows the
concentration of potassium ions to build up within the neuron.
Because of the unequal distribution of these and other ions, the
neuronal cell membrane carries an electrical charge typically up to
50 to 70 millivolts, or even greater than 70 millivolts in certain
instances, with the negative charge on the inner face of the cell
membrane. If the membrane is briefly short-circuited by a change in
its ionic permeability, sodium ions rush inwards and potassium ions
rush outwards for a brief instant. This rapid movement of ions
short-circuits an adjacent region of the cell membrane so that the
cycle is propagated along the membrane. This self-propagating ionic
and electrical change is known as an action potential. An example
of an action potential is shown in FIG. 1, and the effect of
various ions channels and/or transporters opening during the
compound action potential is shown in FIG. 2A. Further, FIG. 2B
illustrates the effects of the compound action potential on the
permeability of specific ion channels. As described in further
detail below, the neuromodulation and mapping systems described
herein can be used to selectively target certain ion channels to
map the ensuing action potential cascade and/or neuromodulate the
specific ion channel to stop the subsequent action potentials
(e.g., by transmitting a stimulating or modulating signal having a
threshold frequency associated with the target). Once an action
potential has passed a region of a membrane, an equilibrium is
restored so that the neuron is ready for the next action potential.
During this brief restoration period (known as the refractory
period) the membrane does not respond to any further stimuli.
Action potentials are normally carried in only one direction, which
is away from the origin of the action potential. All action
potentials are identical after initiation. Thus, the information
carried by the neurons is coded by the number and frequency pattern
of the action potentials.
[0028] F wave is phenomena defined by the second of two voltage
changes observed after electrical stimulation is applied to a nerve
and can be used to measure nerve conduction velocity and/or other
physiological parameters. For example, an electrical stimulus can
be applied at a distal portion of a nerve so that the impulse
travels both distally (orthodromic, i.e., towards a muscle fiber)
and proximally (antidromic, i.e., back to ganglionic bodies of the
motor neurons of the central nervous system (CNS)). When the
orthodromic stimulus reaches the muscle fiber, it elicits a first,
strong response (muscle contraction). When the antidromic stimulus
reaches the motor neuron cell bodies, some of the motor neurons
backfire to cause a counterflow orthodromic wave that travels
distally down the nerve towards the muscle. This stimulus evokes a
small, second compound muscle action potential that defines the F
wave.
[0029] Epithelia form a tight monolayer harboring a stable and
sufficient transepithelial resistance. The active secretion or
absorption of charged salts, such as sodium (Na.sup.+) and chloride
(Cl.sup.-) ions, induces a potential difference across the
epithelial surface that can be measured as a voltage. For example,
the bioelectric potential can be measured by using a high-impedance
voltmeter between two electrodes of a neuromodulation device, such
as the neuromodulation device described below, or a separate
voltage monitoring device.
[0030] In some embodiments, the incident electromagnetic field
(e.g., detected via the electrodes) with soft and hard tissues
within the nasal, paranasal space (e.g., the nasal mucosa,
sub-mucosa composition, periosteum, and bony plates) depends on the
local geometry and the dielectric properties of those systems. Due
to the structures of the soft and hard tissues, large distinctions
exist in both the relative conductivity and the relative
permittivity of the soft and hard tissues. As such, a threshold
level of frequency can be identified to differentiate the "deeper"
mucosal tissue on the turbinates from the "shallow" tissue off the
turbinates.
Selected Embodiments of Systems for Anatomical Mapping and
Therapeutic Neuromodulation
[0031] FIG. 3A is a partially schematic view of a system 300 for
detecting anatomical structures and therapeutic nasal
neuromodulation configured in accordance with an embodiment of the
present technology, and FIG. 3B is an enlarged isometric view of a
distal portion of the system 300 configured in accordance with an
embodiment of the present technology. As shown in FIG. 3A, the
system 300 includes a detection and modulation catheter or device
302 ("device 302"), a console 304, and a cable 306 extending
therebetween. The device 302 includes a shaft 308 having a proximal
portion 308a, a distal portion 308b, a handle 310 at a proximal
portion 308a of the shaft 308, and an evaluation/modulation
assembly or element 312 at the distal portion 308b of the shaft
308. The shaft 308 is configured to locate the distal portion 308b
intraluminally at a treatment or target site, such as within a
nasal region proximate to postganglionic parasympathetic nerves
that innervate the nasal mucosa. The target site may be a region,
volume, or area in which the target nerves are located and may
differ in size and shape depending upon the anatomy of the patient.
For example, the target site may be a 3-5 cm.sup.2 area inferior to
the sphenopalatine foramen ("SPF"). In other embodiments, the
target site may be larger, smaller, and/or located elsewhere in the
nasal cavity to target the desired neural fibers. The
evaluation/modulation assembly 312 can include at least one
electrode 344 configured to therapeutically modulate postganglionic
parasympathetic nerves via electromagnetic energy (e.g., RF
energy). In certain embodiments, for example, the
evaluation/modulation assembly 312 can therapeutically modulate the
postganglionic parasympathetic nerves branching from the
pterygopalatine ganglion and innervating the nasal region and nasal
mucosa, such as parasympathetic nerves (e.g., the posterior nasal
nerves) traversing the SPF, accessory foramen, and microforamina of
a palatine bone. The electrodes 344 and/or other sensing elements
of the evaluation/modulation assembly 312 can further be configured
to detect one or more physiological parameters in an interest zone
before, during, and/or after therapeutic neuromodulation for
identifying the target site, targeting the treatment to the
patient's anatomy, and/or evaluating the efficacy of the
treatment.
[0032] In various embodiments, the evaluation/modulation assembly
312 can include one or more sensing elements 314, such as one or
more of the following sensors: a pressure sensor, a temperature
sensor (e.g., thermocouples, thermistors, etc.), a flow sensor
(e.g., a Doppler velocity sensor, an ultrasonic flow meter, etc.),
a flow rate sensor, a complex impedance sensor, a dielectric
sensor, a chemical sensor, a bio-sensing element, a voltmeter, an
electrochemical sensor, a hemodynamic sensor, an optical sensor,
and/or other suitable sensing devices. The sensor(s) and/or the
electrodes 344 can be connected to one or more wires (not shown;
e.g., copper wires) extending through the shaft 308 to transmit
signals to and from the electrodes 344 and/or the sensor(s). In
some embodiments, the electrodes 344 and/or the sensor(s) can
communicate wirelessly with various components of the system
300.
[0033] In some embodiments, the evaluation/modulation assembly 312
can include energy delivery elements configured to provide
therapeutic neuromodulation using modalities other than RF energy,
such as cryotherapeutic cooling, ultrasound energy (e.g., high
intensity focused ultrasound ("HIFU") energy), microwave energy
(e.g., via a microwave antenna), direct heating, high and/or low
power laser energy, mechanical vibration, and/or optical power. In
further embodiments, the evaluation/modulation assembly 312 can be
configured to deliver chemicals or drugs to the target site to
chemically ablate or embolize the target nerves. For example, the
evaluation/modulation assembly 312 can include a needle applicator
extending through an access portion of the shaft 308 and/or a
separate introducer, and the needle applicator can be configured to
inject a chemical into the target site to therapeutically modulate
the target nerves, such as botox, alcohol, guanethidine, ethanol,
phenol, a neurotoxin, or another suitable agent selected to alter,
damage, or disrupt nerves.
[0034] The device 302 can be operatively coupled to the console 304
via a wired connection (e.g., via the cable 306) and/or a wireless
connection. The console 304 can be configured to control, monitor,
supply, and/or otherwise support operation of device 302. The
console 304 can further be configured to generate a selected form
and/or magnitude of energy for delivery to tissue or nerves at the
target site via the evaluation/modulation assembly 312, and
therefore the console 304 may have different configurations
depending on the treatment modality of the device 302. For example,
when device 302 is configured for electrode-based,
heat-element-based, and/or transducer-based treatment, the console
304 includes an energy generator 316 configured to generate RF
energy (e.g., monopolar, bipolar, or multi-polar RF energy), pulsed
electrical energy, microwave energy, optical energy, ultrasound
energy (e.g., intraluminally-delivered ultrasound and/or HIFU),
direct heat energy, radiation (e.g., infrared, visible, and/or
gamma radiation), and/or another suitable type of energy. When the
device 302 is configured for cryotherapeutic treatment, the console
304 can include a refrigerant reservoir (not shown), and can be
configured to supply the device 302 with refrigerant. Similarly,
when the device 302 is configured for chemical-based treatment
(e.g., drug infusion), the console 304 can include a chemical
reservoir (not shown) and can be configured to supply the device
302 with one or more chemicals.
[0035] In some embodiments, the device 302 can further include a
channel 324 extending along at least a portion of the shaft 308 and
a port 326 at the distal portion 308b of the shaft in communication
with the port 326. In certain embodiments, the channel 324 is a
fluid pathway to deliver a fluid to the distal portion 308b of the
shaft 308 via the port 326. For example, the channel 324 can
deliver saline solution or other fluids to rinse the intraluminal
nasal pathway during delivery of the evaluation/modulation assembly
312, flush the target site before applying therapeutic
neuromodulation to the target site, and/or deliver fluid to the
target site during energy delivery to reduce heating or cooling of
the tissue adjacent to the electrodes 344. In other embodiments,
the channel 324 allows for drug delivery to the treatment site. For
example, a needle (not shown) can project through the port 326 to
inject or otherwise deliver a nerve block, a local anesthetic,
and/or other pharmacological agent to tissue at the target site. In
some embodiments, the channel 324 allows for vapor and/or smoke
removal or evacuation from the treatment site.
[0036] As further shown in FIG. 3A, the system 300 can include a
controller 318 communicatively coupled to the device 302. In the
illustrated embodiment, the controller 318 is housed in the console
304. In other embodiments, the controller 318 can be carried by the
handle 310 of the device 302, the cable 306, an independent
component, and/or another portion of the system 300. The controller
318 can be configured to initiate, terminate, and/or adjust
operation of one or more components (e.g., the electrodes 344) of
the device 302 directly and/or via the console 304. The controller
318 can be configured to execute an automated control algorithm
and/or to receive control instructions from an operator (e.g., a
clinician). For example, the controller 318 and/or other components
of the console 304 (e.g., memory) can include a computer-readable
medium carrying instructions, which when executed by the controller
318, cause the evaluation/modulation assembly 312 to perform
certain functions (e.g., apply energy in a specific manner, detect
impedance, detect temperature, detect nerve locations or anatomical
structures, etc.). A memory includes one or more of various
hardware devices for volatile and non-volatile storage, and can
include both read-only and writable memory. For example, a memory
can comprise 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, and so forth. A memory is not
a propagating signal divorced from underlying hardware; a memory is
thus non-transitory.
[0037] The console 304 can also be configured to provide feedback
to an operator before, during, and/or after a treatment procedure
via mapping/evaluation/feedback algorithms 320. For example, the
mapping/evaluation/feedback algorithms 320 can be configured to
provide information associated with the location of nerves at the
treatment site, the location of other anatomical structures (e.g.,
vessels) at the treatment site, the temperature at the treatment
site during monitoring and modulation, and/or the effect of the
therapeutic neuromodulation on the nerves at the treatment site. In
certain embodiments, the mapping/evaluation/feedback algorithm 320
can include features to confirm efficacy of the treatment and/or
enhance the desired performance of the system 300. For example, the
mapping/evaluation/feedback algorithm 320, in conjunction with the
controller 318 and the evaluation/modulation assembly 312, can be
configured to monitor neural activity and/or temperature at the
treatment site during therapy and automatically shut off the energy
delivery when the neural activity and/or temperature reaches a
predetermined threshold (e.g., a threshold reduction in neural
activity, a threshold maximum temperature when applying RF energy,
or a threshold minimum temperature when applying cryotherapy). In
other embodiments, the mapping/evaluation/feedback algorithm 320,
in conjunction with the controller 318, can be configured to
automatically terminate treatment after a predetermined maximum
time, a predetermined maximum impedance or resistance rise of the
targeted tissue (i.e., in comparison to a baseline impedance
measurement), a predetermined maximum impedance of the targeted
tissue), and/or other threshold values for biomarkers associated
with autonomic function. This and other information associated with
the operation of the system 300 can be communicated to the operator
via a display 322 (e.g., a monitor, touchscreen, user interface,
etc.) on the console 304 and/or a separate display (not shown)
communicatively coupled to the console 304.
[0038] In various embodiments, the evaluation/modulation assembly
312 and/or other portions of the system 300 can be configured to
detect various bioelectric-parameters of the tissue at the target
site, and this information can be used by the
mapping/evaluation/feedback algorithms 320 to determine the anatomy
at the target site (e.g., tissue types, tissue locations,
vasculature, bone structures, foramen, sinuses, etc.), locate
neural structures, differentiate between different types of neural
structures, map the anatomical and/or neural structure at the
target site, and/or identify neuromodulation patterns of the
evaluation/modulation assembly 312 with respect to the patient's
anatomy. For example, the evaluation/modulation assembly 312 can be
used to detect resistance, complex electrical impedance, dielectric
properties, temperature, and/or other properties that indicate the
presence of neural fibers and/or other anatomical structures in the
target region. In certain embodiments, the evaluation/modulation
assembly 312, together with the mapping/evaluation/feedback
algorithms 320, can be used to determine resistance (rather than
impedance) of the tissue (i.e., the load) to more accurately
identify the characteristics of the tissue. The
mapping/evaluation/feedback algorithms 320 can determine resistance
of the tissue by detecting the actual power and current of the load
(e.g., via the electrodes 344). In some embodiments, the system 300
provides resistance measurements with a high degree of accuracy and
a very high degree of precision, such as precision measurements to
the hundredths of an Ohm (e.g., 0.01.OMEGA.) for the range of
1-50.OMEGA. The high degree of resistance detection accuracy
provided by the system 300 allows for the detection sub-microscale
structures, including the firing of neural structures, differences
between neural structures and other anatomical structures (e.g.,
blood vessels), and event different types of neural structures.
This information can be analyzed by the mapping/evaluation/feedback
algorithms and/or the controller 318 and communicated to the
operator via a high resolution spatial grid (e.g., on the display
322) and/or other type of display to identify neural structures and
other anatomy at the treatment site and/or indicate predicted
neuromodulation regions based on the ablation pattern with respect
to the mapped anatomy.
[0039] The device 302 provides access to target sites deep within
the nasal region, such as at the immediate entrance of
parasympathetic fibers into the nasal cavity to therapeutically
modulate autonomic activity within the nasal cavity. In certain
embodiments, for example, the device 302 can position the
evaluation/modulation assembly 312 inferior to the SPF at the site
of access foramen and/or microforamina as described in U.S. patent
application Ser. No. 15/153,217, filed May 10, 2016, which is
incorporated herein by reference in its entirety. By manipulating
the proximal portion 308a of the shaft 308 from outside the
entrance of the nose, a clinician may advance the shaft 308 through
the tortuous intraluminal path through the nasal cavity and
remotely manipulate the distal portion 308b of the shaft 308 via
the handle 310 to position the evaluation/modulation assembly 312
at the target site. In certain embodiments, the shaft 308 can be a
steerable device (e.g., a steerable catheter) with a 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 can further be
configured to articulate in at least two different directions. For
example, the steerable shaft 308 can include dual pull wire rings
that allow a clinician to form the distal portion 308b of the shaft
308 into an "S"-shape to correspond to the anatomy of the nasal
region. In other embodiments, the articulating shaft 308 can be
made from a substantially rigid material (e.g., a metal material)
and include rigid links at the distal portion 308b of the shaft 308
that resist deflection, yet allow for a small bend radius (e.g., a
5 mm bend radius, a 4 mm bend radius, a 3 mm bend radius or less).
In further embodiments, the steerable shaft 308 may be a laser-cut
tube made from a metal and/or other suitable material. The
laser-cut tube can include one or more pull wires operated by the
clinician to allow the clinician to deflect the distal portion 308b
of the shaft 308 to navigate the tortuous nasal anatomy to the
target site.
[0040] In various embodiments, the distal portion 308b of the shaft
308 is guided into position at the target site via a guidewire (not
shown) using an over-the-wire (OTW) or a rapid exchange (RX)
technique. For example, the distal end of the evaluation/modulation
assembly 312 can include a channel for engaging the guidewire.
Intraluminal delivery of the evaluation/modulation assembly 312 can
include inserting the guide wire into an orifice in communication
with the nasal cavity (e.g., the nasal passage or mouth), and
moving the shaft 308 and/or the evaluation/modulation assembly 312
along the guide wire until the evaluation/modulation assembly 312
reaches a target site (e.g., inferior to the SPF). In further
embodiments, the device 302 can be configured for delivery via a
guide catheter or introducer sheath (not shown) with or without
using a guide wire. Image guidance (e.g., via an endoscope,
computed tomography (CT), fluoroscopy, ultrasound, optical
coherence tomography (OCT), and/or combinations thereof) may be
used to aid the clinician's positioning and manipulation of the
distal portion 308b of the shaft 308 and the evaluation/modulation
assembly 312.
[0041] During delivery to the target site, the
evaluation/modulation assembly 312 can be arranged in a low-profile
delivery state and, once at the target site, the
evaluation/modulation assembly 312 can be transformed to an
expanded state (shown in FIGS. 3A and 3B) via manipulation of the
handle 310 such that the evaluation/modulation assembly 312
contacts tissue at the target site for physiological parameter
detection and/or neural modulation. As shown in the enlarged view
of the evaluation/modulation assembly 312 in FIG. 3B, the
evaluation/modulation assembly 312 can include a plurality of
struts 340 that are spaced apart from each other to form a frame or
basket 342 when the evaluation/modulation assembly 312 is in the
expanded state. The struts 340 can carry one or more of the
electrodes 344 and/or other energy delivery elements. In the
expanded state, the struts 340 can position at least two of the
electrodes 344 against tissue at a target site or zone of interest
within the nasal region (e.g., proximate to the palatine bone
inferior to the SPF). The electrodes 344 can apply bipolar or
multi-polar radiofrequency (RF) energy to the target site to detect
bioelectric properties of the treatment site and/or to
therapeutically modulate postganglionic parasympathetic nerves that
innervate the nasal mucosa proximate to the target site. In various
embodiments, the electrodes 344 can be configured to apply pulsed
RF energy with a desired duty cycle (e.g., 1.00 second on/0.50
seconds off), varying power levels, and/or varying pulse durations
and frequency to regulate the temperature increase in the target
tissue. As shown in FIG. 3B, the distal end portion of the basket
includes a double inflection to enhance or maximize the contact
surface area of the strut 340 to adjacent tissue (e.g., a mucosal
wall).
[0042] In the embodiment illustrated in FIG. 3B, the basket 342
includes eight branches 346 spaced radially apart from each other
to form at least a generally spherical structure, and each of the
branches 346 includes two struts 340 positioned adjacent to each
other. In other embodiments, however, the basket 342 can include
fewer than eight branches 346 (e.g., two, three, four, five, six,
or seven branches) or more than eight branches 346. In further
embodiments, each branch 346 of the basket 342 can include a single
strut 340, more than two struts 340, and/or the number of struts
340 per branch 346 can vary. In still further embodiments, the
branches 346 and struts 340 can form baskets or frames having other
suitable shapes for placing the electrodes 344 in contact with
tissue at the target site. For example, when in the expanded state,
the struts 340 can form an ovoid shape, a hemispherical shape, a
cylindrical structure, a pyramid structure, and/or other suitable
shapes. The structural shape of the basket 342 can also be
segmented, replicated, and/or miniaturized duplications of one or
more suitable shapes.
[0043] As shown in FIG. 3B, the evaluation/modulation assembly 312
can further include an internal or interior support member 348 that
extends distally from the distal portion 308b of the shaft 308. A
distal end portion 350 of the support member 348 can support the
distal end portions of the struts 340 to form the desired basket
shape. For example, as shown in FIG. 3, the struts 340 can extend
distally from the distal potion 308b of the shaft 308 and the
distal end portions of the struts 340 can attach to the distal end
portion 350 of the support member 348. In certain embodiments, the
support member 348 can include an internal channel (not shown)
through which flexible electrical connectors (e.g., wires) coupled
to the electrodes 344 and/or other electrical features of the
evaluation/modulation assembly 312 can run. In various embodiments,
the internal support member 348 can also carry an electrode (not
shown) at the distal end portion 350 and/or along the length of the
support member 348.
[0044] The individual struts 340 can be made from a resilient
material, such as a shape-memory material (e.g., Nitinol), that
allows the struts 340 to self-expand into the desired shape of the
basket 342 when in the expanded state. The struts 340 can also be
made from composite wire structures with enhanced core materials
for conductivity and resistivity performance to enhance the signals
detected by the electrodes 344. In other embodiments, the struts
340 can be made from other suitable materials and/or the
evaluation/modulation assembly 312 can be mechanically expanded via
a balloon or by proximal movement of the support member 348. The
basket 342 and the associated struts 340 can have sufficient
rigidity to support the electrodes 344 and position or press the
electrodes 344 against tissue at the target site. In addition, the
expanded basket 342 can press against surrounding anatomical
structures proximate to the target site (e.g., the turbinates, the
palatine bone, etc.) and the individual struts 340 can at least
partially conform to the shape of the adjacent anatomical
structures to anchor the therapeutic element 312 at the treatment
site during energy delivery. This expansion and conformability of
the struts 340 can facilitate placing the electrodes 344 in contact
with the surrounding tissue at the target site.
[0045] Each strut 340 can include one or more electrodes 344 (e.g.,
two electrodes 344, three electrodes 344, four electrodes 344, five
electrodes 344, more than five electrodes 344), and/or the number
of electrodes 344 on the different struts 340 can vary. In some
embodiments, for example, each strut 340 can include five
electrodes 344 such that each branch 346 includes ten electrodes
344 that can define five adjacent electrode pairs, although the
electrodes 344 may be independently activated and paired with
different electrodes 344 of the branch 346 and/or other branches
346. For example, the electrodes 344 can have a length of 0.25-2.25
mm (e.g., 0.75 mm), a spacing along each strut 340 of about 0.5-3.5
mm (e.g., 1.5 mm), and an inter-pairing spacing of about 1.5-4.0 mm
(e.g., 2 mm). In other embodiments the electrode sizing and spacing
can differ. In some embodiments, it may be beneficial to have the
electrodes positioned or spaced differently along the struts 340
than shown in FIG. 3B and/or asymmetrically positioned electrodes
on one or more of the struts 340. For example, a mid-portion of the
struts 340 may include a higher density of electrodes 344 than the
proximal or distal portions of the struts 340. Such an asymmetric
distribution of electrodes 344 may be particularly advantageous for
mapping functions. This may be achieved through the placing of the
electrode array in a known spatial configuration, and mapping
electro-anatomical characteristics in a composition of multiple
(high-density) activation sequence mappings in multiple planes
and/or multiple or varying depths that incorporates variations in
the impedance of different tissue types, including different
cellular or functional constructs, and at different waveform
frequencies (as described in greater detail below).
[0046] In certain embodiments, each electrode 344 can be operated
independently of the other electrodes 344. For example, each
electrode can be individually activated and the polarity and
amplitude of each electrode can be selected by an operator or a
control algorithm executed by the controller 318 (FIG. 3A). The
selective independent control of the electrodes 344 allows the
evaluation/modulation assembly 312 to detect information and
deliver RF energy to highly customized regions. For example, a
select portion of the electrodes 344 can be activated to target
specific neural fibers in a specific region while the other
electrodes 344 remain inactive. In certain embodiments, for
example, electrodes 344 may be activated across the portion of the
basket 342 that is adjacent to tissue at the target site, and the
electrodes 344 that are not proximate to the target tissue can
remain inactive to avoid applying energy to non-target tissue. In
addition, the electrodes 344 can be individually activated to
stimulate or therapeutically modulate certain regions in a specific
pattern at different times (e.g., via multiplexing), which
facilitates detection of anatomical parameters across a zone of
interest and/or regulated therapeutic neuromodulation.
[0047] The electrodes 344 can be electrically coupled to the energy
generator 316 (FIG. 3B) via wires (not shown) that extend from the
electrodes 344, through the shaft 308, and to the energy generator
316. When each of the electrodes 344 is independently controlled,
each electrode 344 couples to a corresponding wire that extends
through the shaft 308. This allows each electrode 344 to be
independently activated for stimulation or neuromodulation to
provide precise ablation patterns and/or individually detected via
the console 304 (FIG. 3A) to provide information specific to each
electrode 344 for neural or anatomical detection and mapping. In
other embodiments, multiple electrodes 344 can be controlled
together and, therefore, multiple electrodes 344 can be
electrically coupled to the same wire extending through the shaft
308. The energy generator 316 (FIG. 3A) and/or components (e.g., a
control module) operably coupled thereto can include custom
algorithms to control the activation of the electrodes 344. For
example, the RF generator can deliver RF power at about 200-300 W
to the electrodes 344, and do so while activating the electrodes
344 in a predetermined pattern selected based on the position of
the evaluation/modulation assembly 312 relative to the treatment
site and/or the identified locations of the target nerves. In other
embodiments, the energy generator 316 delivers power at lower
levels (e.g., less than 1 W, 1-5 W, 5-15 W, 15-50 W, 50-150 W,
etc.) for stimulation and/or higher power levels. For example, the
energy generator 316 can be configured to delivery stimulating
energy pulses of 1-3 W via the electrodes 344 to stimulate specific
targets in the tissue.
[0048] As shown in FIG. 3B, the evaluation/modulation assembly 312
can further include one or more temperature sensors 352 disposed on
the struts 340 and/or other portions of the evaluation/modulation
assembly 312 and electrically coupled to the console 304 (FIG. 3A)
via wires (not shown) that extend through the shaft 308. In various
embodiments, the temperature sensors 352 can be positioned
proximate to the electrodes 344 to detect the temperature at the
interface between tissue at the target site and the electrodes 344.
In other embodiments, the temperature sensors 352 can penetrate the
tissue at the target site (e.g., a penetrating thermocouple) to
detect the temperature at a depth within the tissue. The
temperature measurements can provide the operator or the system
with feedback regarding the effect of the therapeutic
neuromodulation on the tissue. For example, in certain embodiments
the operator may wish to prevent or reduce damage to the tissue at
the treatment site (e.g., the nasal mucosa), and therefore the
temperature sensors 352 can be used to determine if the tissue
temperature reaches a predetermined threshold for irreversible
tissue damage. Once the threshold is reached, the application of
therapeutic neuromodulation energy can be terminated to allow the
tissue to remain intact and avoid significant tissue sloughing
during wound healing. In certain embodiments, the energy delivery
can automatically terminate based on an the
mapping/evaluation/feedback algorithm 320 (FIG. 3A) stored on the
console 304 (FIG. 3A) operably coupled to the temperature sensors
352.
[0049] In other embodiments, the evaluation/modulation assembly 312
can have different configurations than that shown in FIG. 3B. For
example, the evaluation/modulation assembly 312 can include
structures and components similar to those described in U.S. patent
application Ser. No. 15/153,217, filed May 10, 2016, and
incorporated herein in its entirety. In various embodiments, for
example, the evaluation/modulation assembly 312 may include an
expandable balloon that has plurality of electrodes disposed
thereon with spacing selected to enhance sensing resolution. The
balloon can be positioned within the basket 342 and/or be a
standalone structure. The balloon may also be configured to act as
a heat sink by being configured to receive a cooling agent or media
to reduce the heating of tissue adjacent to the electrodes 344
during preventing the surfaces electrodes from contributing to
thermal damage from ablation.
[0050] Referring to FIG. 3A and 3B together, when the
evaluation/modulation assembly 312 is positioned at the target
site, therapeutic modulation may be applied via the electrodes 344
and/or other features of the evaluation/modulation assembly 312 to
precise, localized regions of tissue to induce one or more desired
therapeutic neuromodulating effects to disrupt parasympathetic
motor sensory function. The evaluation/modulation assembly 312 can
selectively target postganglionic parasympathetic fibers that
innervate the nasal mucosa at a target or treatment site proximate
to or at their entrance into the nasal region. For example,
evaluation/modulation assembly 312 can be positioned to apply
therapeutic neuromodulation at least proximate to the SPF to
therapeutically modulate nerves entering the nasal region via the
SPF, accessory foramen and/or microforamina (e.g., in the palatine
bone). The purposeful application of the energy at the target site
may achieve therapeutic neuromodulation along all or at least a
portion of posterior nasal neural fibers entering the nasal region.
The therapeutic neuromodulating effects are generally a function
of, at least in part, power, time, and contact between the energy
delivery elements and the adjacent tissue. For example, in certain
embodiments therapeutic neuromodulation of autonomic neural fibers
are produced by applying RF energy in pulsed or constant waveforms
at a power of about 2-20 W (e.g., 5 W, 7 W, 10 W, etc.) for a time
period of about 1-20 seconds (e.g., 5-10 seconds, 8-10 seconds,
10-12 seconds, etc.).
[0051] The therapeutic neuromodulating effects may include partial
or complete denervation via thermal ablation and/or non-ablative
thermal alteration or damage (e.g., via sustained heating and/or
resistive heating). Desired thermal heating effects may include
raising the temperature of target neural 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 the 45.degree. C.
isotherm in which the applicants have identified that modulations
of parasympathetic nerves begin to occur. It is expected that
therapeutic neuromodulation can be achieved at the 45.degree. C.
isotherm, the 55.degree. C. isotherm, at the 60.degree. C.,
isotherms between 45.degree. C. and 60.degree. C., and/or higher
isotherms. Accordingly, the system 300 can be configured to apply
therapeutic neuromodulation until the temperature at the target
site reaches a threshold of 45.degree. C., 55.degree. C.,
60.degree. C., a value between 45.degree. C. and 60.degree. C., or
higher than 60.degree. C. In various embodiments, delivering the
neuromodulation energy creates an electric field-depth that causes
ionic agitation to disrupt neural activity and/or tissue
temperatures resulting in a lesion size for changing the
conductive/impedance/electrical properties of the tissue types
within the region of interest.
[0052] Hypothermic effects may also provide neuromodulation. For
example, a cryotherapeutic applicator may be used to cool tissue at
a target site to provide therapeutically-effective direct cell
injury (e.g., necrosis), vascular injury (e.g., starving the cell
from nutrients by damaging supplying blood vessels), and sublethal
hypothermia with 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 can include cooling a structure positioned at or near
tissue such that the tissue is effectively cooled to a depth where
the targeted postganglionic parasympathetic nerves reside. For
example, the cooling structure is cooled to the extent that it
causes therapeutically effective, cryogenic posterior nasal nerve
modulation.
[0053] In certain embodiments, the system 300 can determine the
locations and/or morphology of neural structures and/or other
anatomical structures before therapy such that the therapeutic
neuromodulation can be applied to precise regions including target
neural structures, while avoiding negative effects on non-target
structures, such as blood vessels. As described in further detail
below, the system 300 can detect various bioelectrical parameters
in an interest zone (e.g., within in the nasal cavity) to determine
the location and morphology of various neural structures (e.g.,
different types of neural structures, neuronal directionality,
etc.) and/or other tissue (e.g., glandular structures, vessels,
bony regions, etc.). In some embodiments, the system 300 is
configured to measure bioelectric potential. To do so, one or more
of the electrodes 344 is placed in contact with an epithelial
surface at a region of interest (e.g., a treatment site).
Electrical stimuli (e.g., constant or pulsed currents at one or
more frequencies) are applied to the tissue by one or more
electrodes 344 at or near the treatment site, and the voltage
and/or current differences at various different frequencies between
various pairs of electrodes 344 of the evaluation/modulation
assembly 312 may be measured to produce a spectral profile or map
of the detected bioelectric potential, which can be used to
identify different types of tissues (e.g., vessels, neural
structures, and/or other types of tissue) in the region of
interest. For example, current (i.e., direct or alternating
current) can be applied to a pair of electrodes 344 adjacent to
each other and the resultant voltages and/or currents between other
pairs of adjacent electrodes 344 are measured. It will be
appreciated that the current injection electrodes 344 and
measurement electrodes 344 need not be adjacent, and that modifying
the spacing between the two current injection electrodes 344 can
affect the depth of the recorded signals. For example,
closely-spaced current injection electrodes 344 provided recorded
signals associated with tissue deeper from the surface of the
tissue than further spaced apart current injection electrodes 344
that provide recorded signals associated with tissue at shallower
depths. Recordings from electrode pairs with different spacings may
be merged to provide additional information on depth and
localization of anatomical structures.
[0054] Further, complex impedance and/or resistance measurements of
the tissue at the region of interest can be detected directly from
current-voltage data provided by the bioelectric potential
measurements while differing levels of frequency currents are
applied to the tissue (e.g., via the evaluation/modulation assembly
312), and this information can be used to map the neural and
anatomical structures by the use of frequency differentiation
reconstruction. Applying the stimuli at different frequencies will
target different stratified layers or cellular bodies or clusters.
At high signal frequencies (e.g., electrical injection or
stimulation), for example, cell membranes of the neural structures
do not impede current flow, and the current passes directly through
the cell membranes. In this case, the resultant measurement (e.g.,
impedance, resistance, capacitance, and/or induction) is a function
of the intracellular and extracellular tissue and liquids. At low
signal frequencies, the membranes impede current flow to provide
different defining characteristics of the tissues, such as the
shapes of the cells or cell spacing. The stimulation frequencies
can be in the megahertz range, in the kilohertz range (e.g.,
400-500 kHz, 450-480 kHz, etc.), and/or other frequencies attuned
to the tissue being stimulated and the characteristics of the
device being used. The detected complex impedance or resistances
levels from the zone of interest can be displayed to the user
(e.g., via the display 322) to visualize certain structures based
on the stimulus frequency. For example, FIG. 6 is an illustration
of neural impedance mapping at three different regions of tissue
and at five different depths, with the neural structures 609 being
identified by a different color or shading so that the clinician
can locate suitable neural targets. Similar complex impedance
mapping can be provided for different structures (e.g.,
vessels).
[0055] Further, the inherent morphology and composition of the
anatomical structures in the nasal region react differently to
different frequencies and, therefore, specific frequencies can be
selected to identify very specific structures. For example, the
morphology or composition of targeted structures for anatomical
mapping may depend on whether the cells of tissue or other
structure are membranonic, stratified, and/or annular. In various
embodiments, the applied stimulation signals can have predetermined
frequencies attuned to specific neural structures, such as the
level of myelination and/or morphology of the myelination. For
example, second axonal parasympathetic structures are poorly
myelinated than sympathetic nerves or other structures and,
therefore, will have a distinguishable response (e.g., complex
impedance, resistance, etc.) with respect to a selected frequency
than sympathetic nerves. Accordingly, applying signals with
different frequencies to the target site can distinguish the
targeted parasympathetic nerves from the non-targeted sensory
nerves, and therefore provide highly specific target sites for
neural mapping before or after therapy and/or neural evaluation
post-therapy. In some embodiments, the neural and/or anatomical
mapping includes measuring data at a region of interest with at
least two different frequencies to identify certain anatomical
structures such that the measurements are taken first based on a
response to an injection signal having a first frequency and then
again based on an injection signal having a second frequency
different from the first. For example, there are two frequencies at
which hypertrophied (i.e., disease-state characteristics)
sub-mucosal targets have a different electrical conductivity or
permittivity compared to "normal" (i.e., healthy) tissue. Complex
conductivity may be determined based on one or more measured
physiological parameters (e.g., complex impedance, resistance,
dielectric measurements, dipole measurements, etc.) and/or
observance of one or more confidently known attributes or
signatures. Furthermore, the system 300 can also apply
neuromodulation energy via the electrodes 344 at one or more
predetermined frequencies attuned to a target neural structure to
provide highly targeted ablation of the selected neural structure
associated with the frequency(ies). This highly targeted
neuromodulation also reduces the collateral effects of
neuromodulation therapy to non-target sites/structures (e.g., blood
vessels) because the targeted signal (having a frequency tuned to a
target neural structure) will not have the same modulating effects
on the non-target structures.
[0056] Accordingly, bioelectric properties, such as complex
impedance and resistance, can be used by the system 300 before,
during, and/or after neuromodulation therapy to guide one or more
treatment parameters. For example, before, during, and/or after
treatment, impedance or resistance measurements may be used to
confirm and/or detect contact between one or more electrodes 344
and the adjacent tissue. The impedance or resistance measurements
can also be used to detect whether the electrodes 344 are placed
appropriately with respect to the targeted tissue type by
determining whether the recorded spectra have a shape consistent
with the expected tissue types and/or whether serially collected
spectra were reproducible. In some embodiments, impedance or
resistance measurements may be used to identify a boundary for the
treatment zone (e.g., specific neural structures that are to be
disrupted), anatomical landmarks, anatomical structures to avoid
(e.g., vascular structures or neural structures that should not be
disrupted), and other aspects of delivering energy to tissue.
[0057] The bioelectric information can be used to produce a
spectral profile or map of the different anatomical features
tissues at the target site, and the anatomical mapping can be
visualized in a 3D or 2D image via the display 322 and/or other
user interface to guide the selection of a suitable treatment site.
This neural and anatomical mapping allows the system 300 to
accurately detect and therapeutically modulate the postganglionic
parasympathetic neural fibers that innervate the mucosa at the
numerous neural entrance points into the nasal cavity. Further,
because there are not any clear anatomical markers denoting the
location of the SPF, accessory foramen, and microforamina, the
neural mapping allows the operator to identify and therapeutically
modulate nerves that would otherwise be unidentifiable without
intricate dissection of the mucosa. In addition, anatomical mapping
also allows the clinician to identify certain structures that the
clinician may wish to avoid during therapeutic neural modulation
(e.g., certain arteries). The neural and anatomical bioelectric
properties detected by the system 300 can also be used during and
after treatment to determine the real-time effect of the
therapeutic neuromodulation on the treatment site. For example, the
mapping/evaluation/feedback algorithms 320 can also compare the
detected neural locations 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.
[0058] In various embodiments, the system 300 can also be
configured to map the expected therapeutic modulation patterns of
the electrodes 344 at specific temperatures and, in certain
embodiments, take into account tissue properties based on the
anatomical mapping of the target site. For example, the system 300
can be configured to map the ablation pattern of a specific
electrode ablation pattern at the 45.degree. C. isotherm, the
55.degree. C. isotherm, the 65.degree. C. isotherm, and/or other
temperature/ranges (e.g., temperatures ranging from 45.degree. C.
to 70.degree. C. or higher) depending on the target site and/or
structure.
[0059] FIGS. 4A-4C illustrate three-dimensional views of such
projected ablation patterns of the electrodes 344 of the
evaluation/modulation assembly 312 (FIG. 3A) configured in
accordance with embodiments of the present technology. The ablation
pattern mapping defines a region of influence 405 (shown in broken
lines) that each electrode 344 has on the surrounding tissue. The
region of influence 405 may correspond to the region of tissue that
would be exposed to therapeutically modulating energy based on a
defined electrode activation pattern. In the illustrated
embodiment, the ablation pattern mapping corresponds to a device
that includes five activated electrodes 344 on each strut 340 (FIG.
3B), but the ablation pattern mapping can be used to illustrate the
ablation pattern of any number of electrodes 344, any geometry of
the electrode layout, and/or any ablation activation protocol
(e.g., pulsed activation, multi-polar/sequential activation,
etc.).
[0060] Referring to FIG. 4A, in some embodiments the ablation
pattern may be configured such that each electrode 344 has a region
of influence 405 surrounding only the individual electrode 344
(i.e., a "dot" pattern). In other embodiments, the ablation pattern
may be such that two or more electrodes 344 may link together to
form a sub-grouped regions of influence 405 (FIG. 4B) that define
peanut-like or linear shapes between two or more electrodes 344. In
further embodiments, the ablation pattern can result in a more
expansive or contiguous pattern in which the region of influence
405 extends along multiple electrodes 344 (e.g., along each strut
340 (FIG. 3B)). In still further embodiments, the ablation pattern
may result in different regions of influence depending upon the
electrode activation pattern, phase angle, target temperature,
pulse duration, device structure, and/or other treatment
parameters. The three-dimensional views of the ablation patterns
(e.g., as shown in FIGS. 4A-4C) can be output to the display 322
(FIG. 3A) and/or other user interfaces to allow the clinician to
visualize the changing regions of influence 405 based on different
durations of energy application, different electrode activation
sequences (e.g., multiplexing), different pulse sequences,
different temperature isotherms, and/or other treatment parameters.
This information can be used to determine the appropriate ablation
algorithm for a patient's specific anatomy (as determined via the
system 300 of FIG. 3A). In other embodiments, the three-dimensional
visualization of the regions of influence 405 can be used to
illustrate the regions from which the electrodes 344 detect data
when measuring bioelectrical properties for anatomical mapping. In
this embodiment, the three dimensional visualization can be used to
determine which electrode activation pattern should be used to
determine the desired properties (e.g., impedance, resistance,
etc.) in the desired area. In certain embodiments, it may be better
to use dot assessments (e.g., FIG. 4A), whereas in other
embodiments it may be more appropriate to detect information from
linear or larger contiguous regions (e.g., FIGS. 4B and 4C).
[0061] In some embodiments, the mapped ablation pattern is
superimposed on the anatomical mapping to identify what structures
(e.g., neural structures, vessels, etc.) will be therapeutically
modulated or otherwise affected by the therapy. FIG. 5, for
example, is an illustration of a predicted or planned
neuromodulation zone 507 (shown in broken lines) in relation to
previously identified anatomical structures in a zone of interest
in accordance with embodiments of the present technology. For
example, the illustration shows numerous neural structures 509a-b
and, based on the predicted neuromodulation zone 507, identifies
which neural structures are expected to be therapeutically
modulated. As shown in FIG. 5, the expected therapeutically
modulated neural structures 509a are shaded to differentiate them
from the non-affected neural structures 509b. In other embodiments,
the expected therapeutically modulated neural structures 509a can
be differentiated from the non-affected neural structures 509b
using different colors and/or other indicators. In further
embodiments, the predicted neuromodulation zone 507 and surrounding
anatomy (based on anatomical mapping) can be shown in a three
dimensional view (e.g., similar to FIGS. 4A-4C) and/or include
different visualization features (e.g., color-coding to identify
certain anatomical structures, bioelectric properties of the target
tissue, etc.). The combined predicted ablation pattern and
anatomical mapping (e.g., as shown in FIG. 5) can be output to the
display 322 (FIG. 3A) and/or other user interfaces to allow the
clinician to select the appropriate ablation algorithm for a
patient's specific anatomy.
[0062] The imaging provided by the system 300 and shown in FIGS.
4A-6 allows the clinician to visualize the ablation pattern before
therapy and adjust the ablation pattern to target specific
anatomical structures while avoiding others to prevent collateral
effects. For example, the clinician can select a treatment pattern
to avoid blood vessels, thereby reducing exposure of the vessel to
the therapeutic neuromodulation energy. This reduces the risk of
damaging or rupturing vessels and, therefore, prevents immediate or
latent bleeding. Further, the selective energy application provided
by the neural mapping reduces collateral effects of the therapeutic
neuromodulation, such as tissue sloughing off during wound healing
(e.g., 1-3 weeks post ablation), thereby reducing the aspiration
risk associated with the neuromodulation procedure.
[0063] The system 300 can be further configured to apply
neuromodulation energy (via the electrodes 344) at specific
frequencies attuned to the target neural structure and, therefore,
specifically target desired neural structures over non-target
structures. For example, the specific neuromodulation frequencies
can correspond to the frequencies identified as corresponding to
the target structure during neural mapping. As described above, the
inherent morphology and composition of the anatomical structures
react differently to different frequencies. Thus, frequency-tuned
neuromodulation energy tailored to a target structure does not have
the same modulating effects on non-target structures. More
specifically, applying the neuromodulation energy at the
target-specific frequency causes ionic agitation in the target
neural structure, leading to differentials in osmotic potentials of
the targeted neural structures and dynamic changes in neuronal
membronic potentials (resulting from the difference in
intra-cellular and extra-cellular fluidic pressure). This causes
degeneration, possibly resulting in vacuolar degeneration and,
eventually, necrosis at the target neural structure, but is not
expected to functionally affect at least some non-target structures
(e.g., blood vessels). Accordingly, the system 300 can use the
neural-structure specific frequencies to both (1) identify the
locations of target neural structures to plan electrode ablation
configurations (e.g., electrode geometry and/or activation pattern)
that specifically focus the neuromodulation on the target neural
structure; and (2) apply the neuromodulation energy at the
characteristic neural frequencies to selectively ablate the neural
structures responsive to the characteristic neural frequencies. For
example, the evaluation/modulation assembly 312 of the system 300
may selectively stimulate and/or modulate parasympathetic fibers,
sympathetic fibers, sensory fibers, alpha/beta/delta fibers,
C-fibers, anoxic terminals of one or more of the foregoing,
insulated over non-insulated fibers (regions with fibers), and/or
other neural structures. In some embodiments, the system 300 may
also selectively target specific cells or cellular regions during
anatomical mapping and/or therapeutic modulation, such as smooth
muscle cells, sub-mucosal glands, goblet cells, stratified cellular
regions within the nasal mucosa. Therefore, the system 300 provides
highly selective neuromodulation therapy specific to targeted
neural structures, and reduces the collateral effects of
neuromodulation therapy to non-target structures (e.g., blood
vessels).
[0064] FIG. 7 is a block diagram illustrating a method 700 of
anatomical mapping and therapeutic neuromodulation in accordance
with embodiments of the present technology. The method 700 is
described below with respect to the system 300 described above with
reference to FIGS. 3A-3B, but the method 700 may be implemented
using other suitable systems for anatomical evaluation and
neuromodulation therapy. As shown in FIG. 7, the method 700
includes expanding an evaluation and modulation device at a zone of
interest ("interest zone"), such as in a portion of the nasal
cavity (block 705). For example, the evaluation/modulation assembly
312 can be expanded such that at least some of the electrodes 344
are placed in contact with mucosal tissue at the interest zone. The
expanded device can then take bioelectric measurements via the
electrodes 344 and/or other sensors to ensure that the desired
electrodes are in proper contact with the tissue at the interest
zone (block 710). In some embodiments, for example, the system 300
detects the impedance and/or resistance across pairs of the
electrodes 344 to confirm that the desired electrodes have
appropriate surface contact with the tissue and that all of the
electrodes are 344 functioning properly.
[0065] The method 700 continues by optionally applying an
electrical stimulus to the tissue (block 715), and detecting
bioelectric properties of the tissue to establish baseline norms of
the tissue (block 720). For example, the method 700 can include
measuring resistance, complex impedance, current, voltage, nerve
firing rate, neuromagnetic field, muscular activation, and/or other
parameters that are indicative of the location and/or function of
neural structures and/or other anatomical structures (e.g.,
glandular structures, blood vessels, etc.). In some embodiments,
the electrodes 344 send one or more stimulation signals (e.g.,
pulsed signals or constant signals) to the interest zone to
stimulate neural activity and initiate action potentials (block
715). The stimulation signal can have a frequency attuned to a
specific target structure (e.g., a specific neural structure, a
glandular structure, a vessel) that allows for identification of
the location of the specific target structure. The specific
frequency of the stimulation signal is a function of the host
permeability and, therefore, applying the unique frequency alters
the tissue attenuation and the depth into the tissue the RF energy
will penetrate. For example, lower frequencies typically penetrate
deeper into the tissue than higher frequencies.
[0066] Pairs of the non-stimulating electrodes 344 of the
evaluation/modulation assembly 312 can then detect one or more
bioelectric properties of the tissue that occur in response to the
stimulus, such as impedance or resistance. For example, an array of
electrodes (e.g., the electrodes 344) can be selectively paired
together an a desired pattern (e.g., multiplexing the electrodes
344) to detect the bioelectric properties at desired depths and/or
across desired regions to provide a high level of spatial awareness
at the interest zone. In certain embodiments, the electrodes 344
can be paired together in a time-sequenced manner according to an
algorithm (e.g., provided by the mapping/evaluation/feedback
algorithms 320). In various embodiments, stimuli can be injected
into the tissue at two or more different frequencies, and the
resultant bioelectric responses (e.g., action potentials) in
response to each of the injected frequencies can be detected via
various pairs of the electrodes 344. For example, an anatomical or
neural mapping algorithm can cause the evaluation/modulation
assembly 312 to deliver pulsed RF energy at specific frequencies
between different pairs of the electrodes 344 and the resultant
bioelectric response can be recorded in a time sequenced rotation
until the desired interest zone is adequately mapped (i.e.,
"multiplexing"). For example, the evaluation/modulation assembly
312 can deliver stimulation energy at a first frequency via
adjacent pairs of the electrodes 344 for a predetermined time
period (e.g., 1-50 milliseconds), and the resultant bioelectric
activity (e.g., resistance) can be detected via one or more other
pairs of electrodes 344 (e.g., spaced apart from each other to
reach varying depths within the tissue). The evaluation/modulation
assembly 312 can then apply stimulation energy at a second
frequency different from the first frequency, and the resultant
bioelectric activity can be detected via the other electrodes. This
can continue when the interest zone has been adequately mapped at
the desired frequencies. As described in further detail below, in
some embodiments the baseline tissue bioelectric properties (e.g.,
nerve firing rate) are detected using static detection methods
(without the injection of a stimulation signal).
[0067] After detecting the baseline bioelectric properties, the
information can be used to map anatomical structures and/or
functions at the interest zone (block 725). For example, the
bioelectric properties detected by the electrodes 344 can be amazed
via the mapping/evaluation/feedback algorithms 320, and an
anatomical map can be output to a user via the display 322. In some
embodiments, complex impedance, dielectric, or resistance
measurements can be used to map parasympathetic nerves and,
optionally, identify neural structures in a diseased state of
hyperactivity. The bioelectric properties can also be used to map
other non-target structures and the general anatomy, such as blood
vessels, bone, and/or glandular structures. The anatomical
locations can be provided to a user (e.g., on the display 322) as a
two-dimensional map (e.g., illustrating relative intensities as
shown in FIG. 6, illustrating specific sites of potential target
structures as shown in FIG. 5) and/or as a three-dimensional image.
This information can be used to differentiate structures on a
submicron, cellular level and identify very specific target
structures (e.g., hyperactive parasympathetic nerves). The method
700 can also predict the ablation patterns of the
evaluation/modulation assembly 312 based on different electrode
neuromodulation protocol (e.g., as shown in FIGS. 4A-4C) and,
optionally, superimpose the predicted neuromodulation patterns onto
the mapped anatomy to indicate to the user which anatomical
structures will be affected by a specific neuromodulation protocol
(e.g., as shown in FIG. 5). For example, when the predicted
neuromodulation pattern is displayed in relation to the mapped
anatomy, a clinician can determine whether target structures will
be appropriately ablated and whether non-target structures (e.g.,
blood vessels) will be undesirably exposed to the therapeutic
neuromodulation energy. Thus, the method 700 can be used for
planning neuromodulation therapy to locate very specific target
structures, avoid non-target structures, and select electrode
neuromodulation protocols.
[0068] Once the target structure is located and a desired electrode
neuromodulation protocol has been selected, the method 700
continues by applying therapeutic neuromodulation to the target
structure (block 740). The neuromodulation energy can be applied to
the tissue in a highly targeted manner that forms micro-lesions to
selectively modulate the target structure, while avoiding
non-targeted blood vessels and allowing the surrounding tissue
structure to remain healthy for effective wound healing. In some
embodiments, the neuromodulation energy can be applied in a pulsed
manner, allowing the tissue to cool between modulation pulses to
ensure appropriate modulation without undesirably affecting
non-target tissue. In some embodiments, the neuromodulation
algorithm can deliver pulsed RF energy between different pairs of
the electrodes 344 in a time sequenced rotation until
neuromodulation is predicted to be complete (i.e.,
"multi-plexing"). For example, the evaluation/modulation assembly
312 can deliver neuromodulation energy (e.g., having a power of
5-10 W (e.g., 7 W, 8 W, 9W) and a current of about 50-100 mA) via
adjacent pairs of the electrodes 344 until at least one of the
following conditions is met: (a) load resistance reaches a
predefined maximum resistance (e.g., 350.OMEGA.); (b) a
thermocouple temperature associated with the electrode pair reaches
a predefined maximum temperature (e.g., 80.degree. C.); or (c) a
predetermined time period has elapsed (e.g., 10 seconds). After the
predetermined conditions are met, the evaluation/modulation
assembly 312 can move to the next pair of electrodes in the
sequence, and the neuromodulation algorithm can terminate when all
of the load resistances of the individual pairs of electrodes is at
or above a predetermined threshold (e.g., 300.OMEGA.). In various
embodiments, the RF energy can be applied at a predetermined
frequency (e.g., 450-500 kHz) and is expected to initiate ionic
agitation of the specific target structure, while avoiding
functional disruption of non-target structures.
[0069] During and/or after neuromodulation therapy, the method
continues by detecting and, optionally, mapping the post-therapy
bioelectric properties of the target site (block 740). This can be
performed in a similar manner as described above with respect to
blocks 715-725. The post-therapy evaluation can indicate if the
target structures (e.g., hyperactive parasympathetic nerves) were
adequately modulated or ablated (block 745). If the target
structures are not adequately modulated (i.e., if neural activity
is still detected in the target structure and/or the neural
activity has not decreased), the method 700 can continue by again
applying therapeutic neuromodulation to the target (block 735). If
the target structures were adequately ablated, the neuromodulation
procedure can be completed (block 750).
Selected Embodiments of Detection of Anatomical Structures and
Function
[0070] Various embodiments of the present technology can include
features that measure bio-electric, dielectric, and/or other
properties of tissue at target sites to determine the presence,
location, and/or activity of neural structures and other anatomical
structures and, optionally, map the locations of the detected
neural structures and/or other anatomical structures. For example,
the present technology can be used to detect glandular structures
and, optionally, their mucoserous functions and/or other functions.
The present technology can also be configured to detect vascular
structures (e.g., arteries) and, optionally, their arterial
functions, volumetric pressures, and/or other functions. The
mapping features discussed below can be incorporated into any the
system 300 (FIGS. 3A and 3B) and/or any other devices disclosed
herein to provide an accurate depiction of nerves at the target
site.
[0071] Neural and/or anatomical detection can occur (a) before the
application of a therapeutic neuromodulation energy to determine
the presence or location of neural structures and other anatomical
structures (e.g., blood vessels, glands, etc.) at the target site
and/or record baseline levels of neural activity; (b) during
therapeutic neuromodulation to determine the real-time effect of
the energy application on the neural fibers at the treatment site;
and/or (c) after therapeutic neuromodulation to confirm the
efficacy of the treatment on the targeted structures (e.g., nerves
glands, etc.). This allows for the identification of very specific
anatomical structures (even to the micro-scale or cellular level)
and, therefore, provides for highly targeted neuromodulation. This
enhances the efficacy and efficiency of the neuromodulation
therapy. In addition, the anatomical mapping reduces the collateral
effects of neuromodulation therapy to non-target sites.
Accordingly, the targeted neuromodulation inhibits damage or
rupture of blood vessels (i.e., inhibits undesired bleeding) and
collateral damage to tissue that may be of concern during wound
healing (e.g., when damage tissue sloughs off of the wall of the
nasal wall).
[0072] In certain embodiments, the systems disclosed herein can use
bioelectric measurements, such as impedance, resistance, voltage,
current density, and/or other parameters (e.g., temperature) to
determine the anatomy, in particular the neural, glandular, and
vascular anatomy, at the target site. The bioelectric properties
can be detected after the transmission of a stimulus (e.g., an
electrical stimulus, such as RF energy delivered via the electrodes
344 of FIGS. 3A-3B; i.e., "dynamic" detection) and/or without the
transmission of a stimulus (i.e., "static" detection).
[0073] Dynamic measurements include various embodiments to excite
and/or detect primary or secondary effects of neural activation
and/or propagation. Such dynamic embodiments involve the heightened
states of neural activation and propagation and use this dynamic
measurement for nerve location and functional identification
relative to the neighboring tissue types. For example, a method of
dynamic detection can include: (1) delivering stimulation energy to
a treatment site via a treatment device (e.g., the
evaluation/modulation assembly 312) to excite parasympathetic
nerves at the treatment site; (2) measuring one or more
physiological parameters (e.g., resistance, impedance, etc.) at the
treatment site via a measuring/sensing array of the treatment
device (e.g., the electrodes 344); (4) based on the measurements,
identifying the relative presence and position of parasympathetic
nerves at the treatment site; and (5) delivering ablation energy to
the identified parasympathetic nerves to block the detected
para-sympathetic nerves.
[0074] Static measurements include various embodiments associated
with specific native properties of the stratified or cellular
composition at or near the treatment site. The static embodiments
are directed to inherent biologic and electrical properties of
tissue types at or near the treatment site, the stratified or
cellular compositions at or near the treatment site, and
contrasting both foregoing measurements with tissue types adjacent
the treatment site (and that are not targeted for neuromodulation).
This information can be used to localize specific targets (e.g.,
parasympathetic fibers) and non-targets (e.g., vessels, sensory
nerves, etc.). For example, a method of static detection can
include: (1) before ablation, utilizing a measuring/sensing array
of a treatment device (e.g., the electrodes 344) to determine one
or more baseline physiological parameters; (2) geometrically
identifying inherent tissue properties within a region of interest
based on the measured physiological parameters (e.g., resistance,
impedance, etc.); (3) delivering ablation energy to one or more
nerves within the region of via treatment device interest; (4)
during the delivery of the ablation energy, determining one or more
mid-procedure physiological parameters via the measuring/sensing
array; and (5) after the delivery of ablation energy, determining
one or more post-procedure physiological parameters via the
measurement/sensing array to determine the effectiveness of the
delivery of the ablation energy on blocking the nerves that
received the ablation energy.
[0075] After the initial static and/or dynamic detection of
bioelectric properties, the location of anatomical features can be
used to determine where the treatment site(s) should be with
respect to various anatomical structures for therapeutically
effective neuromodulation of the targeted parasympathetic nasal
nerves. The bioelectric and other physiological properties
discussed herein can be detected via electrodes (e.g., the
electrodes 344 of the evaluation/modulation assembly 312 of FIGS.
3A and 3B), and the electrode pairings on a device (e.g.,
evaluation/modulation assembly 312) can be selected to obtain the
bioelectric data at specific zones or regions and at specific
depths of the targeted regions. The specific properties detected at
or surrounding target neuromodulation sites and associated methods
for obtaining these properties are described below. These specific
detection and mapping methods discussed below are described with
reference to the system 300 of FIGS. 3A and 3B, although the
methods can be implemented on other suitable systems and devices
that provide for anatomical identification, anatomical mapping
and/or neuromodulation therapy.
Neural Identification and Mapping
[0076] In many neuromodulation procedures, it is beneficial to
identify the portions of the nerves that fall within a zone and/or
region of influence (referred to as the "interest zone") of the
energy delivered by a neuromodulation device 302 (FIG. 3A), as well
as the relative three-dimensional position of the neural structures
relative to the neuromodulation device 302. Characterizing the
portions of the neural structures within the interest zone and/or
determining the relative positions of the neural structures within
the interest zone enables the clinician to (1) selectively activate
target neural structures over non-target structures (e.g., blood
vessels), and (2) sub-select specific targeted neural structures
(e.g., parasympathetic nerves) over non-target neural structures
(e.g., sensory nerves, subgroups of neural structures, neural
structures having certain compositions or morphologies). The target
structures (e.g., parasympathetic nerves) and non-target structures
(e.g., blood vessels, sensory nerves, etc.) can be identified based
on the inherent signatures of specific structures, which are
defined by the unique morphological compositions of the structures
and the bioelectrical properties associated with these
morphological compositions. For example, unique, discrete
frequencies can be associated with morphological compositions and,
therefore, be used to identify certain structures. The target and
non-target structures can also be identified based on relative
bioelectrical activation of the structures to sub-select specific
neuronal structures. Further, target and non-target structures can
be identified by the differing detected responses of the structures
to a tailored injected stimuli. For example, the systems described
herein can detect the magnitude of response of structures and the
difference in the responses of anatomical structures with respect
to differing stimuli (e.g., stimuli injected at different
frequencies).
[0077] At least for purposes of this disclosure, a nerve can
include the following portions that are defined based on their
respective orientations relative to the interest zone: terminating
neural structures (e.g., terminating axonal structures), branching
neural structures (e.g., branching axonal structures), and
travelling neural structures (e.g., travelling axonal structures).
For example, terminating neural structures enter the zone but do
not exit. As such, terminating neural structures are terminal
points for neuronal signaling and activation. Branching neural
structures are nerves that enter the interest zone and increase
number of nerves exiting the interest zone. Branching neural
structures are typically associated with a reduction in relative
geometry of nerve bundle. Travelling neural structures are nerves
that enter the interest zone and exit the zone with no
substantially no change in geometry or numerical value.
[0078] The system 300 can be used to detect voltage, current,
complex impedance, resistance, permittivity, and/or conductivity,
which are tied to the compound action potentials of nerves, to
determine and/or map the relative positions and proportionalities
of nerves in the interest zone. Neuronal cross-sectional area
("CSA") is expected to be due to the increase in axonic structures.
Each axon is a standard size. Larger nerves (in cross-sectional
dimension) have a larger number of axons than nerves having smaller
cross-sectional dimensions. The compound action responses from the
larger nerves, in both static and dynamic assessments, are greater
than smaller nerves. This is at least in part because the compound
action potential is the cumulative action response from each of the
axons. When using static analysis, for example, the system 300 can
directly measure and map impedance or resistance of nerves and,
based on the determined impedance or resistance, determine the
location of nerves and/or relative size of the nerves. In dynamic
analysis, the system 300 can be used to apply a stimulus to the
interest zone and detect the dynamic response of the neural
structures to the stimulus. Using this information, the system 300
can determine and/or map impedance or resistance in the interest
zone to provide information related to the neural positions or
relative nerve sizes. Neural impedance mapping can be illustrated
by showing the varying complex impedance levels at a specific
location at differing cross-sectional depths (e.g., as shown in
FIG. 6). In other embodiments, neural impedance or resistance can
be mapped in a three-dimensional display.
[0079] Identifying the portions and/or relative positions of the
nerves within the interest zone can inform and/or guide selection
of one or more treatment parameters (e.g., electrode ablation
patterns, electrode activation plans, etc.) of the system 300 for
improving treatment efficiency and efficacy. For example, during
neural monitoring and mapping, the system 300 can identify the
directionality of the nerves based at least in part on the length
of the neural structure extending along the interest zone, relative
sizing of the neural structures, and/or the direction of the action
potentials. This information can then be used by the system 300 or
the clinician to automatically or manually adjust treatment
parameters (e.g., selective electrode activation, bipolar and/or
multipolar activation, and/or electrode positioning) to target
specific nerves or regions of nerves. For example, the system 300
can selectively activate specific electrodes 344, electrode
combinations (e.g., asymmetric or symmetric), and/or adjust the
bi-polar or multi-polar electrode configuration. In some
embodiments, the system 300 can adjust or select the waveform,
phase angle, and/or other energy delivery parameters based on the
nerve portion/position mapping and/or the nerve proportionality
mapping. In some embodiments, structure and/or properties of the
electrodes 344 themselves (e.g., material, surface roughening,
coatings, cross-sectional area, perimeter, penetrating, penetration
depth, surface-mounted, etc.) may be selected based on the nerve
portion and proportionality mapping.
[0080] In various embodiments, treatment parameters and/or energy
delivery parameters can be adjusted to target on-axis or near axis
travelling neural structures and/or avoid the activation of
traveling neural structures that are at least generally
perpendicular to the evaluation/modulation assembly 312. Greater
portions of the on-axis or near axis travelling neural structures
are exposed and susceptible to the neuromodulation energy provided
by the evaluation/modulation assembly 312 than a perpendicular
travelling neural structure, which may only be exposed to
therapeutic energy at a discrete cross-section. Therefore, the
evaluation/modulation assembly 312 is more likely to have a greater
effect on the on-axis or near axis travelling neural structures.
The identification of the neural structure positions (e.g., via
complex impedance or resistance mapping) can also allow targeted
energy delivery to travelling neural structures rather than
branching neural structures (typically downstream of the travelling
neural structures) because the travelling neural structures are
closer to the nerve origin and, therefore, more of the nerve is
affected by therapeutic neuromodulation, thereby resulting in a
more efficient treatment and/or a higher efficacy of treatment.
Similarly, the identification of neural structure positions can be
used to target travelling and branching neural structures over
terminal neural structures. In some embodiments, the treatment
parameters can be adjusted based on the detected neural positions
to provide a selective regional effect. For example, a clinician
can target downstream portions of the neural structures if only
wanting to influence partial effects on very specific anatomical
structures or positions.
[0081] In various embodiments, neural locations and/or relative
positions of nerves can be determined by detecting the nerve-firing
voltage and/or current over time. An array of the electrodes 344
can be positioned in contact with tissue at the interest zone, and
the electrodes 344 can measure the voltage and/or current
associated with nerve-firing. This information can optionally be
mapped (e.g., on a display 322) to identify the location of nerves
in a hyper state (i.e., excessive parasympathetic tone). Rhinitis
is at least in part the result of over-firing nerves because this
hyper state drives the hyper-mucosal production and hyper-mucosal
secretion. Therefore, detection of nerve firing rate via voltage
and current measurements can be used to locate the portions of the
interest region that include hyper-parasympathetic neural function
(i.e., nerves in the diseased state). This allows the clinician to
locate specific nerves (i.e., nerves with excessive parasympathetic
tone) before neuromodulation therapy, rather than simply targeting
all parasympathetic nerves (including non-diseased state
parasympathetic nerves) to ensure that the correct tissue is
treated during neuromodulation therapy. Further, nerve firing rate
can be detected during or after neuromodulation therapy so that the
clinician can monitor changes in nerve firing rate to validate
treatment efficacy. For example, recording decreases or elimination
of nerve firing rate after neuromodulation therapy can indicate
that the therapy was effective in therapeutically treating the
hyper/diseased nerves.
[0082] In various embodiments, the system 300 can detect neural
activity using dynamic activation by injecting a stimulus signal
(i.e., a signal that temporarily activates nerves) via one or more
of the electrodes 344 to induce an action potential, and other
pairs of electrodes 344 can detect bioelectric properties of the
neural response. Detecting neural structures using dynamic
activation involves detecting the locations of action potentials
within the interest zone by measuring the discharge rate in neurons
and the associated processes. The ability to numerically measure,
profile, map, and/or image fast neuronal depolarization for
generating an accurate index of activity is a factor in measuring
the rate of discharge in neurons and their processes. The action
potential causes a rapid increase in the voltage across nerve fiber
and the electrical impulse then spreads along the fiber. As an
action potential occurs, the conductance of a neural cell membrane
changes, becoming about 40 times larger than it is when the cell is
at rest. During the action potential or neuronal depolarization,
the membrane resistance diminishes by about 80 times, thereby
allowing an applied current to enter the intracellular space as
well. Over a population of neurons, this leads to a net decrease in
the resistance during coherent neuronal activity, such as chronic
para-sympathetic responses, as the intracellular space will provide
additional conductive ions. The magnitude of such fast changes has
been estimated to have local resistivity changes with recording
near DC is 2.8-3.7% for peripheral nerve bundles (e.g., including
the nerves in the nasal cavity).
[0083] Detecting neural structures using dynamic activation
includes detecting the locations of action potentials within the
interest zone by measuring the discharge rate in neurons and the
associated processes. The basis of each this discharge is the
action potential, during which there is a depolarization of the
neuronal membrane of up to 110 mV or more, lasting approximately 2
milliseconds, and due to the transfer of micromolar quantities of
ions (e.g., sodium and potassium) across the cellular membrane. The
complex impedance or resistance change due to the neuronal membrane
falls from 1000 to 25.OMEGA. cm. The introduction of a stimulus and
subsequent measurement of the neural response can attenuate noise
and improve signal to noise ratios to precisely focus on the
response region to improve neural detection, measurement, and
mapping.
[0084] In some embodiments, the difference in measurements of
physiological parameters (e.g., complex impedance, resistance,
voltage) over time, which can reduce errors, can be used to create
a neural profiles, spectrums, or maps. For example, the sensitivity
of the system 300 can be improved because this process provides
repeated averaging to a stimulus. As a result, the mapping function
outputs can be a unit-less ratio between the reference and test
collated data at a single frequency and/or multiple frequencies
and/or multiple amplitudes. Additional considerations may include
multiple frequency evaluation methods that consequently expand the
parameter assessments, such as resistivity, admittivity, center
frequency, or ratio of extra- to intracellular resistivity.
[0085] In some embodiments, the system 300 may also be configured
to indirectly measure the electrical activity of neural structures
to quantify the metabolic recovery processes that accompany action
potential activity and act to restore ionic gradients to normal.
These are related to an accumulation of ions in the extracellular
space. The indirect measurement of electrical activity can be
approximately a thousand times larger (in the order of millimolar),
and thus are easier to measure and can enhance the accuracy of the
measured electrical properties used to generate the neural
maps.
[0086] The system 300 can perform dynamic neural detection by
detecting nerve-firing voltage and/or current and, optionally,
nerve firing rate over time, in response to an external stimulation
of the nerves. For example, an array of the electrodes 344 can be
positioned in contact with tissue at the interest zone, one or more
of the electrodes 344 can be activated to inject a signal into the
tissue that stimulates the nerves, and other electrodes 344 of the
electrode array can measure the neural voltage and/or current due
to nerve firing in response to the stimulus. This information can
optionally be mapped (e.g., on a display 322) to identify the
location of nerves and, in certain embodiments, identify
parasympathetic nerves in a hyper state (e.g., indicative of
Rhinitis or other diseased state). The dynamic detection of neural
activity (voltage, current, firing rate, etc.) can be performed
before neuromodulation therapy to detect target nerve locations to
select the target site and treatment parameters to ensure that the
correct tissue is treated during neuromodulation therapy. Further,
dynamic detection of neural activity can be performed during or
after neuromodulation therapy to allow the clinician to monitor
changes in neural activity to validate treatment efficacy. For
example, recording decreases or elimination of neural activity
after neuromodulation therapy can indicate that the therapy was
effective in therapeutically treating the hyper/diseased
nerves.
[0087] As described in further detail below with respect to FIG. 9,
in some embodiments a stimulating signal can be delivered to the
vicinity of the targeted nerve via one or more penetrating
electrodes (e.g., microneedles that penetrate tissue) associated
with the evaluation/modulation assembly 312 and/or a separate
device. The stimulating signal generates an action potential, which
causes smooth muscle cells or other cells to contract. The location
and strength of this contraction can be detected via the
penetrating electrode(s) and, thereby, indicate to the clinician
the distance to the nerve and/or the location of the nerve relative
to the stimulating needle electrode. In some embodiments, the
stimulating electrical signal may have a voltage of typically 1-2
mA or greater and a pulse width of typically 100-200 microseconds
or greater. Shorter pulses of stimulation result in better
discrimination of the detected contraction, but may require more
current. The greater the distance between the electrode and the
targeted nerve, the more energy is required to stimulate. The
stimulation and detection of contraction strength and/or location
enables identification of how close or far the electrodes are from
the nerve, and therefore can be used to localize the nerve
spatially. In some embodiments, varying pulse widths may be used to
measure the distance to the nerve. As the needle becomes closer to
the nerve, the pulse duration required to elicit a response becomes
less and less.
[0088] To localize nerves via muscle contraction detection, the
system 300 can vary pulse-width or amplitude to vary the energy
(Energy=pulse-width*amplitude) of the stimulus delivered to the
tissue via the penetrating electrode(s). By varying the stimulus
energy and monitoring muscle contraction via the penetrating
electrodes and/or other type of sensor, the system 300 can estimate
the distance to the nerve. If a large amount of energy is required
to stimulate the nerve/contract the muscle, the
stimulating/penetrating electrode is far from the nerve. As the
stimulating/penetrating electrode, moves closer to the nerve, the
amount of energy required to induce muscle contraction will drop.
For example, an array of penetrating electrodes can be positioned
in the tissue at the interest zone and one or more of the
electrodes can be activated to apply stimulus at different energy
levels until they induce muscle contraction. Using an iterative
process, localize the nerve (e.g., via the
mapping/evaluation/feedback algorithm 320).
[0089] In some embodiments, the system 300 can measure the muscular
activation from the nerve stimulus (e.g., via the electrodes 344)
to determine neural positioning for neural mapping, without the use
of penetrating electrodes. In this embodiment, the treatment device
targets the smooth muscle cells' varicosities surrounding the
submucosal glands and the vascular supply, and then the compound
muscle action potential. This can be used to summate voltage
response from the individual muscle fiber action potentials. The
shortest latency is the time from stimulus artifact to onset of the
response. The corresponding amplitude is measured from baseline to
negative peak and measured in millivolts (mV). Nerve latencies
(mean.+-.SD) in adults typically range about 2-6 milliseconds, and
more typically from about 3.4.+-.0.8 to about 4.0.+-.0.5
milliseconds. A comparative assessment may then be made which
compares the outputs at each time interval (especially pre- and
post-energy delivery) in addition to a group evaluation using the
alternative nasal cavity. This is expected to provide an accurate
assessment of the absolute value of the performance of the neural
functioning because muscular action/activation may be used to infer
neural action/activation and muscle action/activation is a
secondary effect or by-product whilst the neural function is the
absolute performance measure.
[0090] In some embodiments, the system 300 can record a
neuromagnetic field outside of the nerves to determine the internal
current of the nerves without physical disruption of the nerve
membrane. Without being bound by theory, the contribution to the
magnetic field from the current inside the membrane is two orders
of magnitude larger than that from the external current, and that
the contribution from current within the membrane is substantially
negligible. Electrical stimulation of the nerve in tandem with
measurements of the magnetic compound action fields ("CAFs") can
yield sequential positions of the current dipoles such that the
location of the conduction change can be estimated (e.g., via the
least-squares method). Visual representation (e.g., via the display
322) using magnetic contour maps can show normal or non-normal
neural characteristics (e.g., normal can be equated with a
characteristic quadrupolar pattern propagating along the nerve),
and therefore indicate which nerves are in a diseases, hyperactive
state and suitable targets for neuromodulation.
[0091] During magnetic field detection, an array of the electrodes
344 can be positioned in contact with tissue at the interest zone
and, optionally, one or more of the electrodes 344 can be activated
to inject an electrical stimulus into the tissue. As the nerves in
the interest zone fire (either in response to a stimulus or in the
absence of it), the nerve generates a magnetic field (e.g., similar
to a current carrying wire), and therefore changing magnetic fields
are indicative of the nerve nerve-firing rate. The changing
magnetic field caused by neural firing can induce a current
detected by nearby sensor wire (e.g., the sensor 314) and/or wires
associated with the nearby electrodes 344. By measuring this
current, the magnetic field strength can be determined. The
magnetic fields can optionally be mapped (e.g., on a display 322)
to identify the location of nerves and select target nerves (nerves
with excessive parasympathetic tone) before neuromodulation therapy
to ensure that the desired nerves are treated during
neuromodulation therapy. Further, the magnetic field information
can be used during or after neuromodulation therapy so that the
clinician can monitor changes in nerve firing rate to validate
treatment efficacy.
[0092] In other embodiments, the neuromagnetic field is measured
with a Hall Probe or other suitable device, which can be integrated
into the evaluation/modulation assembly 312 and/or part of a
separate device delivered to the interest zone. Alternatively,
rather than measuring the voltage in the second wire, the changing
magnetic field can be measured in the original wire (i.e. the
nerve) using a Hall probe. A current going through the Hall probe
will be deflected in the semi-conductor. This will cause a voltage
difference between the top and bottom portions, which can be
measured. In some aspects of this embodiments, three orthogonal
planes are utilized.
[0093] In some embodiments, the system 300 can be used to induce
electromotive force ("EMF") in a wire (i.e., a frequency-selective
circuit, such as a tunable/LC circuit) that is tunable to resonant
frequency of a nerve. In this embodiment, the nerve can be
considered to be a current carrying wire, and the firing action
potential is a changing voltage. This causes a changing current
which, in turn, causes a changing magnetic flux (i.e., the magnetic
field that is perpendicular to the wire). Under Faraday's Law of
Induction/Faraday's Principle, the changing magnetic flux induces
EMF (including a changing voltage) in a nearby sensor wire (e.g.,
integrated into the evaluation/modulation assembly 312, the sensor
314, and/or other structure), and the changing voltage can be
measured via the system 300.
[0094] In further embodiments, the sensor wire (e.g., the sensor
314) is an inductor and, therefore, provides an increase of the
magnetic linkage between the nerve (i.e., first wire) and the
sensor wire (i.e., second wire), with more turns for increasing
effect. (e.g., V2,rms=V1,rms (N2/N1)). Due to the changing magnetic
field, a voltage is induced in the sensor wire, and this voltage
can be measured and used to estimate current changes in the nerve.
Certain materials can be selected to enhance the efficiency of the
EMF detection. For example, the sensor wire can include a soft iron
core or other high permeability material for the inductor.
[0095] During induced EMF detection, the evaluation/modulation
assembly 312 and/or other device including a sensor wire is
positioned in contact with tissue at the interest zone and,
optionally, one or more of the electrodes 344 can be activated to
inject an electrical stimulus into the tissue. As the nerves in the
interest zone fire (either in response to a stimulus or in the
absence of it), the nerve generates a magnetic field (e.g., similar
to a current carrying wire) that induces a current in the sensor
wire (e.g., the sensor 314). This information can be used to
determine neural location and/or map the nerves (e.g., on a display
322) to identify the location of nerves and select target nerves
(nerves with excessive parasympathetic tone) before neuromodulation
therapy to ensure that the desired nerves are treated during
neuromodulation therapy. EMF information can also be used during or
after neuromodulation therapy so that the clinician can monitor
changes in nerve firing rate to validate treatment efficacy.
[0096] In some embodiments, the system 300 can detect magnetic
fields and/or EMF generated at a selected frequency that
corresponds to a particular type of nerve. The frequency and, by
extension, the associated nerve type of the detected signal can be
selected based on an external resonant circuit. Resonance occurs on
the external circuit when it is matched to the frequency of the
magnetic field of the particular nerve type and that nerve is
firing. In manner, the system 300 can be used to locate a
particular sub-group/type of nerves.
[0097] In some embodiments, the system 300 can include a variable
capacitor frequency-selective circuit to identify the location
and/or map specific nerves (e.g., parasympathetic nerve, sensory
nerve, nerve fiber type, nerve subgroup, etc.). The variable
capacitor frequency-selective circuit can be defined by the sensor
314 and/or other feature of the evaluation/modulation assembly 312.
Nerves have different resonant frequencies based on their function
and structure. Accordingly, the system 300 can include a tunable LC
circuit with a variable capacitor (C) and/or variable inductor (L)
that can be selectively tuned to the resonant frequency of desired
nerve types. This allows for the detection of neural activity only
associated with the selected nerve type and its associated resonant
frequency. Tuning can be achieved by moving the core in and out of
the inductor. For example, tunable LC circuits can tune the
inductor by: (i) changing the number of coils around the core; (ii)
changing the cross-sectional area of the coils around the core;
(iii) changing the length of the coil; and/or (iv) changing the
permeability of the core material (e.g., changing from air to a
core material). Systems including such a tunable LC circuit provide
a high degree of dissemination and differentiation not only as to
the activation of a nerve signal, but also with respect to the
nerve type that is activated and the frequency at which the nerve
is firing.
Anatomical Mapping
[0098] In various embodiments, the system 300 is further configured
to provide minimally-invasive anatomical mapping that uses focused
energy current/voltage stimuli from a spatially localized source
(e.g., the electrodes 344) to cause a change in the conductivity of
the of the tissue at the interest zone and detect resultant
biopotential and/or bioelectrical measurements (e.g., via the
electrodes 344). The current density in the tissue changes in
response to changes of voltage applied by the electrodes 344, which
creates a change in the electric current that can be measured with
the evaluation/modulation assembly 312 and/or other portions of the
system 300. The results of the bioelectrical and/or biopotential
measurements can be used to predict or estimate relative absorption
profilometry to predict or estimate the tissue structures in the
interest zone. More specifically, each cellular construct has
unique conductivity and absorption profiles that can be indicative
of a type of tissue or structure, such as bone, soft tissue,
vessels, nerves, types of nerves, and/or certain neural structures.
For example, different frequencies decay differently through
different types of tissue. Accordingly, by detecting the absorption
current in a region, the system 300 can determine the underlying
structure and, in some instances, to a sub-microscale, cellular
level that allows for highly specialized target localization and
mapping. This highly specific target identification and mapping
enhances the efficacy and efficiency of neuromodulation therapy,
while also enhancing the safety profile of the system 300 to reduce
collateral effects on non-target structures.
[0099] To detect electrical and dielectric tissue properties (e.g.,
resistance, complex impedance, conductivity, and/or, permittivity
as a function of frequency), the electrodes 344 and/or another
electrode array is placed on tissue at an interest region, and an
internal or external source (e.g., the generator 316) applies
stimuli (current/voltage) to the tissue. The electrical properties
of the tissue between the source and the receiver electrodes 344
are measured, as well as the current and/or voltage at the
individual receiver electrodes 344. These individual measurements
can then be converted into an electrical map/image/profile of the
tissue and visualized for the user on the display 322 to identify
anatomical features of interest and, in certain embodiments, the
location of firing nerves. For example, the anatomical mapping can
be provided as a color-coded or gray-scale three-dimensional or
two-dimensional map showing differing intensities of certain
bioelectric properties (e.g., resistance, impedance, etc.), or the
information can be processed to map the actual anatomical
structures for the clinician. This information can also be used
during neuromodulation therapy to monitor treatment progression
with respect to the anatomy, and after neuromodulation therapy to
validate successful treatment. In addition, the anatomical mapping
provided by the bioelectrical and/or biopotential measurements can
be used to track the changes to non-target tissue (e.g., vessels)
due to neuromodulation therapy to avoid negative collateral
effects. For example, a clinician can identify when the therapy
begins to ligate a vessel and/or damage tissue, and modify the
therapy to avoid bleeding, detrimental tissue ablation, and/or
other negative collateral effects.
[0100] Furthermore, the threshold frequency of electric current
used to identify specific targets can subsequently be used when
applying therapeutic neuromodulation energy. For example, the
neuromodulation energy can be applied at the specific threshold
frequencies of electric current that are target neuronal-specific
and differentiated from other non-targets (e.g., blood vessels,
non-target nerves, etc.). Applying ablation energy at the
target-specific frequency results in an electric field that creates
ionic agitation in the target neural structure, which leads to
differentials in osmotic potentials of the targeted neural
structures. These osmotic potential differentials cause dynamic
changes in neuronal membronic potentials (resulting from the
difference in intra-cellular and extra-cellular fluidic pressure)
that lead to vacuolar degeneration of the targeted neural
structures and, eventually, necrosis. Using the highly targeted
threshold neuromodulation energy to initiate the degeneration
allows the system 300 to delivery therapeutic neuromodulation to
the specific target, while surrounding blood vessels and other
non-target structures are functionally maintained.
[0101] In some embodiments, the system 300 can further be
configured to detect bioelectrical properties of tissue by
non-invasively recording resistance changes during neuronal
depolarization to map neural activity with electrical impedance,
resistance, bio-impedance, conductivity, permittivity, and/or other
bioelectrical measurements. Without being bound by theory, when a
nerve depolarizes, the cell membrane resistance decreases (e.g., by
approximately 80.times.) so that current will pass through open ion
channels and into the intracellular space. Otherwise the current
remains in the extracellular space. For non-invasive resistance
measurements, tissue can be stimulated by applying a current of
less than 100 Hz, such as applying a constant current square wave
at 1 Hz with an amplitude less than 25% (e.g., 10%) of the
threshold for stimulating neuronal activity, and thereby preventing
or reducing the likelihood that the current does not cross into the
intracellular space or stimulating at 2 Hz. In either case, the
resistance and/or complex impedance is recorded by recording the
voltage changes. A complex impedance or resistance map or profile
of the area can then be generated (e.g., as shown in FIG. 6).
[0102] For impedance/conductivity/permittivity detection, the
electrodes 344 and/or another electrode array are placed on tissue
at an interest region, and an internal or external source (e.g.,
the generator 316) applies stimuli to the tissue, and the current
and/or voltage at the individual receiver electrodes 344 is
measured. The stimuli can be applied at different frequencies to
isolate different types of nerves. These individual measurements
can then be converted into an electrical map/image/profile of the
tissue and visualized for the user on the display 322 to identify
anatomical features of interest. The neural mapping can also be
used during neuromodulation therapy to select specific nerves for
therapy, monitor treatment progression with respect to the nerves
and other anatomy, and validate successful treatment.
[0103] In some embodiments of the neural and/or anatomical
detection methods described above, the procedure can include
comparing the mid-procedure physiological parameter(s) to the
baseline physiological parameter(s) and/or other,
previously-acquired mid-procedure physiological parameter(s)
(within the same energy delivery phase). Such a comparison can be
used to analyze state changes in the treated tissue. The
mid-procedure physiological parameter(s) may also be compared to
one or more predetermined thresholds, for example, to indicate when
to stop delivering treatment energy. In some embodiments of the
present technology, the measured baseline, mid-, and post-procedure
parameters include a complex impedance. In some embodiments of the
present technology, the post-procedure physiological parameters are
measured after a pre-determined time period to allow the
dissipation of the electric field effects (ionic agitation and/or
thermal thresholds), thus facilitating accurate assessment of the
treatment.
[0104] In some embodiments, the anatomical mapping methods
described above can be used to differentiate the depth of soft
tissues within the nasal mucosa. The depth of mucosa on the
turbinates is great whilst the depth off the turbinate is shallow
and, therefore, identifying the tissue depth in the present
technology also identifies positions within the nasal mucosa and
where precisely to target. Further, by providing the micro-scale
spatial impedance mapping of epithelial tissues as described above,
the inherent unique signatures of stratified layers or cellular
bodies can be used as identifying the region of interest. For
example, different regions have larger or small populations of
specific structures, such as submucosal glands, so target regions
can be identified via the identification of these structures.
[0105] In some embodiments, the system 300 includes additional
features that can be used to detect anatomical structures and map
anatomical features. For example, the system 300 can include an
ultrasound probe for identification of neural structures and/or
other anatomical structures. Higher frequency ultrasound provides
higher resolution, but less depth of penetration. Accordingly, the
frequency can be varied to achieve the appropriate depth and
resolution for neural/anatomical localization. Functional
identification may rely on the spatial pulse length ("SPL")
(wavelength multiplied by number of cycles in a pulse). Axial
resolution (SPL/2) may also be determined to locate nerves.
[0106] In some embodiments, the system 300 can further be
configured to emit stimuli with selective parameters that suppress
rather than fully stimulate neural activity. for example, in
embodiments where the strength-duration relationship for
extracellular neural stimulation is selected and controlled, a
state exists where the extracellular current can hyperpolarize
cells, resulting in suppression rather than stimulation spiking
behavior (i.e., a full action potential is not achieved). Both
models of ion channels, HH and RGC, suggest that it is possible to
hyperpolarize cells with appropriately designed burst extracellular
stimuli, rather than extending the stimuli. This phenomenon could
be used to suppress rather than stimulate neural activity during
any of the embodiments of neural detection and/or modulation
described herein.
Selected Embodiments of Evaluation and Neuromodulation Devices
[0107] FIGS. 8A and 8B are isometric views of a distal portion of a
neuromodulation and mapping device 802 ("device 802") configured in
accordance with an embodiment of the present technology. The device
802 can include various features generally similar to the features
of the device 302 described above with reference to FIGS. 3A and
3B. For example, the device 802 includes an evaluation/modulation
assembly 812 at the distal portion 308b of the shaft 308. The
evaluation/modulation 812 includes a plurality of struts 340 that
form branches 346 and define an expandable frame or basket 342, and
optionally include one or more electrodes 344 disposed on one or
more of the struts 340. As shown in FIGS. 8A and 8B, the device 802
can further include an expandable member 856 (e.g., a balloon)
carried by the support member 348 and expandable within the basket
342. The expandable member 856 can include one or more electrodes
858 that extend in a circumferential pattern across the outer
surface of the expandable member 856. For example, the one or more
electrodes 858 can define a coil shape disposed on the expandable
member 856. The electrodes 858 can be used for detection of
bioelectric features (e.g., complex impedance, resistance, etc.) to
allow for mapping of the anatomy at the interest zone before,
during, and/or after therapeutic neuromodulation via the other
electrodes 344. In other embodiments, the electrodes 858 can be
configured to apply energy for therapeutic neuromodulation.
[0108] As shown in FIG. 8B, the electrode(s) 858 can be positioned
across a substantial portion of the expandable member 856 that
proves an expansive area at which impedance and/or other properties
can be detected across the tissue and, therefore, may provide a
more detailed mapping of the tissue and nerves at the treatment
site. The expandable member 856 can also closely conform to the
adjacent tissue at the zone of interest and, therefore, facilitate
contact between the electrode(s) 858 and the tissue. In other
embodiments, the electrodes 858 can have different configurations
on the outer surface of the expandable member 856. When there are
multiple electrodes 358, the individual electrodes 858 can be
selectively activated at a specific polarity, and therefore the
electrode array can be configured in a variety of static
configurations and a dynamically change sequences (e.g.,
sesquipolar application of current) that may be advantageous for
mapping functions.
[0109] In operation, the expandable member 856 can be inflated or
otherwise expanded (FIG. 8B) to place at least a portion of the
electrodes 858 into contact with tissue at the target site. The
electrodes 858 can measure various bioelectric properties of the
tissue (e.g., impedance, action potentials, etc.) to detect,
locate, and/or map the neural structures and/or other anatomical
structures at the interest zone. In certain embodiments, the
electrodes 344 on the struts 340 and/or a portion of the electrodes
858 on the expandable member 856 can apply a stimulating pulse of
RF energy, and the electrodes 858 can detect the resultant neural
response. After mapping, the expandable member 856 can be deflated
or collapsed (FIG. 8A), and the electrodes 344 on the struts 340
can apply therapeutically effective neuromodulation energy to the
target site. For example, the ablation pattern of the electrodes
344 can be based on the neural locations identified via the
information detected from the sensing electrodes 858 on the
expandable member 856. In other embodiments, the expandable member
856 may remain expanded during neuromodulation, and the electrodes
858 can detect neural activity during the neuromodulation procedure
or the electrodes 858 can themselves be configured to apply
neuromodulation energy to the treatment site. After applying the
neuromodulation energy, the electrodes 858 on the expandable member
856 can again be placed into contact with tissue at the target
site, and used to record bioelectric properties (e.g., impedance,
resistance, voltage, etc.). The detected properties taken before,
during, and/or after neuromodulation can be compared to each other
to determine whether the neuromodulation was therapeutically
effective. If not, the electrodes 344 can again apply therapeutic
neuromodulation energy to the same treatment site, or the
configuration of the active electrodes 344 can be changed to apply
therapeutic neuromodulation energy in a different pattern or
sequence, and/or the evaluation/modulation assembly 812 can be
moved to a different treatment site.
[0110] FIG. 9 is an enlarged isometric view of a distal portion of
a neuromodulation and mapping device 902 ("device 902") configured
in accordance with some embodiments of the present technology. The
device 902 can include various features generally similar to the
features of the device 802 described above with reference to FIGS.
8A and 8B. For example, the device 902 includes an
evaluation/modulation assembly 912 that includes the plurality of
struts 340 (optionally including electrodes 344 disposed thereon)
that form the expandable frame or basket 342 and the expandable
member 856 (e.g., a balloon) inflatable within the basket 342 via
an inflation media (e.g., a fluid, coolant, etc.). As shown in FIG.
9, the expandable member 856 includes one or more protruding or
penetrating electrodes 960 that extend across the outer surface of
the expandable member 856 in a circumferential pattern to define a
three-dimensional microneedle array. The penetrating electrodes 960
can be very small needles and/or other structures with sharp end
portions that penetrate a small depth into adjacent tissue when the
expandable member 856 is expanded. For example, the needle
electrodes 960 may have a tip diameter on the micron level (e.g., 1
micron diameter, 2 micron diameter, 3 micron diameter, 1-20 micron
diameter, etc.), a length of 50-350 microns (e.g., 150 microns, 210
microns, 250 microns, etc.), and/or tips coated in platinum black
and/or other suitable materials. In other embodiments, the
protruding needle electrodes 960 have different sizes, different
material composition, and/or are arranged in different patterns
across the expandable member 856 (e.g., in an asymmetrical pattern)
that facilitate penetration into adjacent tissue and/or detection
of desired tissue parameters. In some embodiments, for example, the
penetrating electrodes 960 can be fabricated by selective
vapor-liquid-solid growth of a silicon wire. In further
embodiments, the penetrating electrodes 960 can define a
microneedle array on a different portion of the device 902 (e.g.,
along the struts 340) and/or on a substrate separate from the
evaluation/modulation assembly 912. For example, the penetrating
electrodes 960 can be positioned on substrate (e.g., a paddle) that
can be pressed into contact with tissue to drive the electrodes 960
a small depth into the tissue. The penetrating electrodes 960 may
also be deployable and/or retractable. In some embodiments, the
penetrating electrodes 960 can be integrated with the metal oxide
semiconductor process for high-performance on-chip electronics
configurations. In some embodiments, the electrodes 344 on the
struts 340 and/or other electrodes on the evaluation/modulation
assembly 912 can be replaced by deployable and/or
protruding/retractable penetrating needle electrodes.
[0111] The electrodes 960 can be used for detection of bioelectric
features (e.g., impedance, resistance, etc.) and/or other
detectable parameters to allow for mapping of the neural and/or
other anatomy at the interest zone before, during, and/or after
therapeutic neuromodulation via the other electrodes 344. In other
embodiments, the penetrating electrodes 960 can be configured to
apply energy for therapeutic neuromodulation. The device 902
requires only a minimal level of invasiveness, but is expected to
provide high spatial resolution and high level of accuracy due to
the broad area covered by the penetrating electrodes, the high
density of the electrodes 960 across the area, and the penetration
into the tissue of interest. In some embodiments, for example, the
output/input signal amplitude ratios may be >90% at about 40 Hz
to about 10 KHz. The device 902 can be used in chronic as well as
acute cases.
[0112] In various embodiments, the expandable member 856 of the
devices 802 and 902 described above with respect to FIGS. 8A-9 can
be used as a drug delivery mechanism for delivering a local
anesthetic pre- or post-procedurally, a neurotoxin (e.g., to
stimulate or modulate nerves at the target site), and/or other
drugs or chemicals. The expandable member 856 can be made from a
porous material with a plurality of openings or voids for drug
expulsion (e.g., eluding drugs disposed within the expandable
member 856). The expandable member 856 can also include drugs
loaded or embedded within the wall of the expandable member 856
such that pressure against the drug-loaded wall by the tissue
causes drug elusion. The neural and anatomical mapping systems and
methods described above can be used to ensure precision and
accuracy of the drug delivery.
[0113] Any of the therapeutic or detection assemblies and devices
disclosed herein may be semi-permanently implanted rather than
connected to a catheter shaft (for temporary delivery to the
treatment site). For implanted embodiments, any of the devices and
methods disclosed herein may be used to obtain feedback to locate
the appropriate implant site, position the device for long-term
implantation, confirm device functionality (e.g., for neural
blocking) in-situ and in real-time, and/or to confirm the
functionality of the implantable device over the lifetime of the
device, the disease, and/or the patient.
[0114] In some embodiments, for example, the evaluation/modulation
assembly 312 (FIG. 3A) is part of an implantable device separate
from the catheter shaft 308 to allow for continued use of the
evaluation/modulation assembly 312 over an extended period of time
(i.e., not only during the procedure). For example, the implantable
device can include a micro-stimulator/modulator (e.g., the
evaluation/modulation 312 with the electrodes 344) that is
permanently or semi-permanently implanted at a treatment site and a
hermetically- or mechanically-sealed controller coupled to the
implantable device. In various embodiments, the implantable device
can include a variable resistive element, a variable capacitive
element, one or more electrodes, and/or fixation or anchoring
elements that position the electrodes against tissue within the
target site (e.g., within the nasal cavity).
[0115] In various embodiments, the implantable device is powered
wirelessly by an external unit spaced apart from the monitoring and
therapeutic assembly and the treatment site. For example, the
external power unit can be worn by the patient, implanted within
the patient (e.g., subdermally, within a cavity, etc.) apart from
the monitoring and therapeutic assembly, and/or otherwise spaced
apart from the treatment site. The device may have a power source
that is not reliant on a battery to avoid additional clinical
intervention. For example, the device may use capacitive coupling
to charge/receive transient charge and/or generation of a magnetic
field to couple to the power unit. In some embodiments, magnetic
resonant coupling may be the connection mechanism regarding
wireless/battery connectivity and coupling.
[0116] The implantable device treats conditions, such as rhinitis,
by electrically modulating the parasympathetic nerve pathway to the
nasal cavity in a similar manner as the system 300 described above
with reference to FIGS. 3A-3B, but may provide neural modulation
and/or anatomical mapping over an extended period of time (e.g.,
outside of a procedure) and may be activated at the onset of a
predefined sensed trigger (e.g., hyperactivity of the mucosal glad
or the parasympathetic nerves). For example, in some embodiments,
the modulation may be delivered in bursts in response to threshold
levels of autonomic activity. In some embodiments, the modulation
may be delivered by a patient in response to symptomatic conditions
associated with the disease state (e.g., allergic symptoms as
perceived by the patient such as hay fever triggers, sneezing,
excessive rhinorrhea, congestion, etc.). The modulation provided by
the implantable device may selectively stimulate or modulate
parasympathetic fibers, sympathetic fibers, sensory fibers,
alpha/beta/delta fibers, C-fibers, anoxic terminals of one or more
of the foregoing, insulated over non-insulated fibers (regions with
fibers), and/or other neural structures. In some embodiments, the
implantable device may selectively target specific cells or
cellular regions, such as smooth muscle cells, sub-mucosal glands,
goblet cells, stratified cellular regions within the nasal mucosa.
These target sites may be identified during anatomical mapping of
neural structures and/or other tissues before implantation of the
device, during implantation, and/or while the device is
implanted.
[0117] The implantable device may be deployed at the target site
via a delivery system (e.g., a catheter) using anatomical mapping
(including neural mapping) for landmarks and positional accuracy as
described above. For example, the delivery system may locate and
eject the implantable device on, partially within, or fully into
the nasal mucosa. The delivery system may be spring loaded, piston
activated, hydraulically activated, and/or otherwise activated to
deploy the implantable device from a distal end of the delivery
system. When the implantable device is configured to be positioned
or otherwise anchored at least partially under the surface of the
nasal walls, the delivery system may include a suction tip, a
needle tip, a dissection tip, a retractable blade with a rotational
member/action, and/or other sharp structures that can form an
opening and an insertion pathway into the soft tissue.
[0118] The implant delivery system may further include linkages or
couplings that connect a distal end portion of the delivery system
(including deployment and access components) to a proximal handle
of the delivery system. Deployment of the implantable device from
the delivery system may be driven by sliders, pistons, depression
buttons, rotational elements, and/or other actuators at the
proximal handle that advance or initiate implantation mechanisms of
the delivery system. In some embodiments, the delivery system may
have a range/stroke limiting mechanism and/or other restrictive
features to limit insertion depth. In some embodiments, the
delivery system may have suction functionality to control
tissue/device interface and the entry angulation of implant. In
some embodiments, the delivery system has an
angulated/circumferential orientation control to selectively
position implant point of entry. The delivery system may also have
micro-positional capabilities to fine-tune positional accuracy
based on neural locations. In some embodiments, the distal tip of
the implantable device is electrically coupled to the delivery
system when the implantable device is in a delivery state (before
deployment) and acts independently or in conjunction with other
features of the delivery system to provide neural mapping and
measuring features and refine positional accuracy. In various
embodiments, the evaluation/modulation assembly 312 (FIG. 3A) and
the device 302 (FIG. 3A) can include similar features as those
described above with respect to the implantable device and the
delivery system.
[0119] The neural and anatomical mapping systems, devices, and
methods, disclosed herein can also be used with respect to
anatomical structures outside of the nasal cavity and/or additional
diseased states, including any peripheral nervous system acute or
chronic disease state. The present technology may be used to assess
and/or monitor (short-term and/or long-term) neural/neuro-muscular
degenerative disease states, intraoperative neuroma-in-continuity,
and the nerve regeneration and degenerative neuromuscular
disorders. Other examples disease states treatable with the present
technology include: acute inflammatory demyelinating polyneuropathy
("AIDP"), Multiple Sclerosis ("MS"), acute motor axonal neuropathy
("MAN"), Lambert-Eaton myasthenic syndrome ("LEMS"), myasthenia
gravis ("MG"), neuromuscular transmission disorders ("NMTD"),
peripheral neurophysiological examination ("PNE"), any
neuromuscular transmission disorder of nerve terminal function,
transmitter production, storage, and/or release, pre-/post-synaptic
membrane structure and function, receptor dynamics, endplate
potentials, propagated muscle action potentials, and others.
Additional Examples
[0120] Several aspects of the present technology are set forth in
the following additional examples.
[0121] 1. A system for detecting anatomical structures and
therapeutic neuromodulation in a nasal region of a human patient,
the system comprising: [0122] a shaft having a proximal portion and
a distal portion, wherein the shaft is configured to locate the
distal portion intraluminally at a target site within a nasal
cavity inferior to a sphenopalatine foramen of the human patient;
[0123] an evaluation/modulation assembly at the distal portion of
the shaft, wherein the evaluation/modulation assembly comprises a
plurality of electrodes configured to emit stimulating energy to
tissue at the target site at frequencies for locating target neural
structures and detect bioelectric properties in response to the
stimulating energy; and [0124] a console including a controller
having a computer-readable medium carrying instructions, which when
executed by the controller, causes the console to map locations of
the target neural structures and causes the evaluation/modulation
assembly to apply therapeutic neuromodulation energy in a
predetermined neuromodulation pattern based on the locations of the
target neural structures.
[0125] 2. The system of example 1 wherein at least a portion of the
plurality of electrodes are configured to apply RF energy at a
predetermined frequency to initiate ionic agitation of the target
neural structure to therapeutically modulate postganglionic
parasympathetic nerves.
[0126] 3. The system of example 1 or 2 wherein at least a portion
of the plurality of electrodes are configured to apply RF energy at
a predetermined frequency to initiate ionic agitation of sub
mucosal structures to therapeutically modulate postganglionic
parasympathetic tone.
[0127] 4. The system of any one of examples 1-3 wherein at least a
portion of the plurality of electrodes are configured to apply RF
energy at a predetermined frequency to initiate vacuolar
degeneration of the target neural structure to therapeutically
modulate postganglionic parasympathetic nerves.
[0128] 5. The system of any one of examples 1-4 wherein: [0129] the
plurality of electrodes are configured to detect bioelectric
properties of non-target anatomical structures at the target site;
[0130] the computer-readable medium carrying instructions, which
when executed by the controller, causes the console to map
locations of non-target anatomical structures and causes the
evaluation/modulation assembly to apply neuromodulation energy in
the predetermined pattern to avoid the locations of the non-target
anatomical structures.
[0131] 6. The system of any one of examples 1-5, further comprising
a display configured to visualize locations of the target neural
structures with respect to a predicted neuromodulation zone defined
by the predetermined neuromodulation pattern.
[0132] 7. The system of any one of examples 1-6 wherein the
plurality of electrodes are configured to detect bioelectric
properties of tissue at the treatment site before therapeutic
neuromodulation, during therapeutic neuromodulation, and/or after
therapeutic neuromodulation.
[0133] 8. The system of example 7 wherein the bioelectric
properties include at least one of complex impedance, resistance,
reactance, capacitance, inductance, permittivity, conductivity,
nerve firing voltage, nerve firing current, magnetic field, and
induced electromotive force.
[0134] 9. The system of any one of examples 1-8 wherein the
evaluation/modulation assembly comprises: [0135] a basket
transformable between a low-profile delivery state and an expanded
state, wherein the basket includes plurality of struts spaced
radially apart from each other when the basket is in the expanded
state, wherein-- [0136] the plurality of electrodes are disposed on
the struts, [0137] the plurality of struts are configured to
position at least two of the electrodes at the target site when the
basket is in the expanded state, and [0138] the electrodes are
configured to apply radiofrequency (RF) energy to the target site
to therapeutically modulate parasympathetic nerves proximate to the
target site.
[0139] 10. The system of example 9 wherein the
evaluation/modulation assembly further comprises: [0140] an
expandable member within the basket and transformable between a
low-profile delivery state to an expanded state, wherein at least a
portion of the plurality of electrodes are disposed on an exterior
surface of the expandable surface.
[0141] 11. The system of example 10 wherein the balloon comprises a
plurality of holes configured to allow perfusion of a drug through
the balloon when the balloon is in the expanded state.
[0142] 12. The system of example 9 wherein the
evaluation/modulation assembly further comprises: [0143] an
expandable member within the basket and transformable between a
low-profile delivery state to an expanded state; and [0144] at
least one sensing electrode disposed on the expandable member,
wherein the sensing electrode defines a coiled shape extending
around a circumferential portion of the expandable member.
[0145] 13. The system of example 9 wherein the
evaluation/modulation assembly further comprises: [0146] an
expandable member within the basket and transformable between a
low-profile delivery state to an expanded state; and [0147] a
plurality of penetrating electrodes disposed on an exterior surface
of the expandable member, wherein the expandable member is
configured to position at least a portion of the penetrating
electrodes a depth into tissue at the target site when the
expandable member is in the expanded state.
[0148] 14. The system of any one of examples 1-13 wherein the
plurality of electrodes includes an array of penetrating electrodes
configured to penetrate a depth into tissue at the target site when
the expandable member is in the expanded state.
[0149] 15. The system of example 14 wherein the penetrating
electrodes are configured to detect muscle contraction in response
to the stimulating energy.
[0150] 16. The system of any one of examples 1-15 wherein the
evaluation/modulation assembly comprises a balloon transformable
between a low-profile delivery state to an expanded state, wherein
at least a portion of the plurality of electrodes are disposed on
the balloon.
[0151] 17. The system of any one of examples 1-16 wherein the
plurality of electrodes are configured to be independently
activated and independently assigned a selective polarity to apply
therapeutic neuromodulation across selected regions of the
evaluation/modulation assembly.
[0152] 18. A system for detecting anatomical structures and
therapeutic neuromodulation in a nasal region of a human patient,
the system comprising: [0153] a shaft having a proximal portion and
a distal portion, wherein the shaft is configured to locate the
distal portion intraluminally at a target site, wherein the target
site is at least one of proximate to the sphenopalatine foramen of
a human patient or inferior to the sphenopalatine foramen; and
[0154] an evaluation/modulation assembly at the distal portion of
the shaft and transformable between a low-profile delivery state
and an expanded state, wherein the evaluation/modulation assembly
comprises a plurality of electrodes configured to be placed into
contact with tissue at the target site when the
evaluation/modulation assembly is in the expanded state and measure
bioelectric properties of tissue at the target site to identify and
locate target anatomical structures and non-target structures; and
[0155] a console including a controller having a computer-readable
medium carrying instructions, which when executed by the
controller, causes the console to map locations of the target
anatomical structures and non-target anatomical structures and
causes the evaluation/modulation assembly to apply therapeutic
neuromodulation energy in a predetermined neuromodulation pattern
based on the locations of the target and non-target anatomical
structures.
[0156] 19. The system of example 18 wherein the instructions, when
executed by the controller, causes the evaluation/modulation
assembly to determine resistance at least proximate to the target
site.
[0157] 20. The system of example 18 or 19 wherein the bioelectric
properties are detected before therapeutic neuromodulation, during
therapeutic neuromodulation, and/or after therapeutic
neuromodulation, and wherein the bioelectric properties include at
least one of complex impedance, resistance, reactance, capacitance,
inductance, permittivity, conductivity, nerve firing voltage, nerve
firing current, magnetic field, and induced electromotive
force.
[0158] 21. The system of any one of examples 18-20 wherein at least
a portion of the plurality of electrodes are configured to apply RF
energy at a predetermined frequency to activate target anatomical
structures for anatomical mapping and/or therapeutic
neuromodulation.
[0159] 22. The system of examples 18-21 wherein the
evaluation/modulation assembly comprises: [0160] a frame
transformable between the low-profile delivery state and the
expanded state, wherein the frame includes plurality of struts
spaced radially apart from each other when the frame is in the
expanded state, and wherein-- [0161] the plurality of electrodes
are disposed on the struts, and [0162] the plurality of struts are
configured to position at least two of the electrodes at the target
site when the frame is in the expanded state.
[0163] 23. The system of examples 18-22 wherein the
evaluation/modulation assembly comprises an expandable member
transformable between the low-profile delivery state to the
expanded state, wherein at least a portion of the plurality of
electrodes are disposed on the expandable member.
[0164] 24. A method of therapeutically modulating nerves in a nasal
region of a human patient, the method comprising: [0165]
intraluminally advancing an evaluation/modulation assembly at a
distal portion of a shaft of a therapeutic device to a target site
within the nasal region, wherein the target site is proximate to
parasympathetic nerves, and wherein the evaluation/modulation
assembly includes a plurality of electrodes; [0166] delivering
stimulation energy to the target site to excite neural structures
at the target site, wherein the stimulation energy is emitted at
one or more frequencies for locating specific target neural
structures; [0167] detecting one or more bioelectric parameters at
the target site via at least a portion of the plurality of
electrodes of the evaluation/modulation assembly; [0168] based on
the detected bioelectric parameters, identifying relative presence
and position of target neural structures at the target site; and
[0169] determining a neuromodulation pattern based on the locations
of the target neural structures to block the detected target neural
structures.
[0170] 25. The method of example 24, further comprising delivering
therapeutic neuromodulation energy based on the predetermined
neuromodulation pattern.
[0171] 26. The method of example 25 wherein delivering therapeutic
neuromodulation energy further comprises delivering RF energy at a
predetermined frequency to initiate ionic agitation of the target
neural structure to therapeutically modulate postganglionic
parasympathetic nerves.
[0172] 27. The method of example 25 wherein delivering therapeutic
neuromodulation energy further comprises delivering RF energy at a
predetermined frequency to initiate ionic agitation of the
submucosal structures to therapeutically modulate postganglionic
parasympathetic nerves.
[0173] 28. The method of example 25 wherein delivering therapeutic
neuromodulation energy further comprises delivering RF energy at a
predetermined frequency to initiate vacuolar degeneration of the
target neural structure to therapeutically modulate postganglionic
parasympathetic nerves.
[0174] 29. The method of any one of examples 24-28 wherein
detecting one or more bioelectric parameters comprises detecting
resistance of the tissue.
[0175] 30. The method of any one of examples 24-29 wherein
detecting one or more bioelectric parameters comprises detecting at
least one of nerve firing voltage and nerve firing current.
[0176] 31. The method of any one of examples 24-30 wherein
detecting one or more bioelectric parameters comprises detecting a
neuromagnetic field at the target site.
[0177] 32. The method of any one of examples 24-31 wherein
detecting one or more bioelectric parameters comprises detecting
induced electromotive force at the target site.
[0178] 33. The method of any one of examples 24-32 wherein: [0179]
detecting one or more bioelectric parameters at the target site
comprises detecting bioelectric parameters of non-target anatomical
structures at the target site; and [0180] the method further
comprises identifying locations of non-target structures at the
target site based on the detected bioelectric parameters.
[0181] 34. The method of any one of examples 24-33, further
comprising visually mapping locations of the target neural
structures with respect to a predicted neuromodulation zone defined
by the predetermined neuromodulation pattern.
[0182] 35. The method of any one of examples 24-34, further
comprising, before delivering stimulation energy, deploying an
array of penetrating electrodes such that at least a portion of the
penetrating electrodes penetrate a depth into the target tissue,
the penetrating electrodes being at least a portion of the
plurality of electrodes and disposed on the evaluation/modulation
assembly.
[0183] 36. The method of example 35 wherein: [0184] detecting one
or more bioelectric parameters at the target site via at least a
portion of the plurality of electrodes of the evaluation/modulation
assembly comprises detecting muscle contraction data in response to
the stimulation energy via the penetrating electrodes; and [0185]
identifying relative presence and position of target neural
structures at the target site comprises mapping locations of target
neural structures based on the detected muscle contraction
data.
[0186] 37. A method of therapeutically modulating nerves in a nasal
region of a human patient, the method comprising: [0187]
intraluminally advancing an evaluation/modulation assembly at a
distal portion of a shaft of a therapeutic device to a target site
within the nasal region, wherein the target site is proximate to
parasympathetic nerves, and wherein the evaluation/modulation
assembly includes a plurality of electrodes; [0188] before
therapeutic neuromodulation, detecting one or more baseline
bioelectric parameters at the target site via at least a portion of
the plurality of electrodes; [0189] geometrically identifying
inherent tissue properties within the target site based on the
detected bioelectric parameters to identify locations of target
structures and non-target structures; [0190] determining a
neuromodulation pattern based on the locations of the target
structures and the non-target structures; and [0191] delivering
therapeutic neuromodulation energy to the target structures in
accordance with the neuromodulation pattern.
[0192] 38. The method of example 37, further comprising: [0193]
during the delivery of the therapeutic neuromodulation energy,
determining one or more mid-procedure bioelectric parameters via
the evaluation/modulation assembly; and [0194] after the delivery
of the therapeutic neuromodulation energy, determining one or more
post-procedure bioelectric parameters via the evaluation/modulation
assembly to determine the effectiveness of the delivery of the
therapeutic neuromodulation energy in blocking the nerves that
received the therapeutic neuromodulation energy.
[0195] 39. The method of example 37 or 38 wherein geometrically
identifying inherent tissue properties within the target site based
on the detected bioelectric parameters comprises detecting nerve
firing rate at the target site.
[0196] 40. The method of any one of examples 37-39 wherein
delivering therapeutic neuromodulation energy to the target
structures in accordance with the neuromodulation pattern comprises
delivering RF energy at a predetermined frequency to initiate ionic
agitation of the target structure to therapeutically modulate
postganglionic parasympathetic nerves.
[0197] 41. The method of any one of examples 37-40 wherein
delivering therapeutic neuromodulation energy to the target
structures in accordance with the neuromodulation pattern comprises
delivering RF energy at a predetermined frequency to initiate ionic
agitation of submucosal structures to therapeutically modulate
postganglionic parasympathetic nerves.
[0198] 42. The method of any one of examples 37-41 wherein
delivering therapeutic neuromodulation energy to the target
structures in accordance with the neuromodulation pattern comprises
delivering RF energy at a predetermined frequency to initiate
vacuolar degeneration of the target structures to therapeutically
modulate postganglionic parasympathetic nerves.
[0199] 43. A device for detecting anatomical structures and
therapeutic neuromodulation in a nasal region of a human patient,
the system comprising: [0200] a shaft having a proximal portion and
a distal portion, wherein the shaft is configured to locate the
distal portion intraluminally at a target site within a nasal
cavity inferior to a sphenopalatine foramen of the human patient;
[0201] an evaluation/modulation assembly at the distal portion of
the shaft, wherein-- [0202] the evaluation/modulation assembly
comprises a plurality of electrodes configured to emit stimulating
energy to tissue at the target site at frequencies for locating
target structures and non-target structures and detect bioelectric
properties in response to the stimulating energy; [0203] the
bioelectric properties are used to map locations of the target
structures and the non-target structures; and [0204] at least a
portion of the plurality of electrodes are configured to apply
therapeutic neuromodulation energy in a predetermined
neuromodulation pattern based on the locations of the target
structures and the non-target structures.
[0205] 44. The device of example 43 wherein at least a portion of
the plurality of electrodes are configured to apply RF energy at a
predetermined frequency to initiate ionic agitation and/or vacuolar
degeneration of the target structures to therapeutically modulate
postganglionic parasympathetic nerves.
CONCLUSION
[0206] This disclosure is not intended to be exhaustive or to limit
the present technology to the precise forms disclosed herein.
Although specific embodiments are disclosed herein for illustrative
purposes, various equivalent modifications are possible without
deviating from the present technology, as those of ordinary skill
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 the
embodiments of the present technology. Although steps of methods
may be presented herein in a particular order, in alternative
embodiments the steps may have another suitable order. Similarly,
certain aspects of the present technology disclosed in the context
of particular embodiments can be combined or eliminated in other
embodiments. Furthermore, while advantages associated with certain
embodiments may have been disclosed in the context of those
embodiments, other embodiments can also exhibit such advantages,
and not all embodiments need necessarily exhibit such advantages or
other advantages disclosed herein to fall within the scope of the
present technology. Accordingly, this disclosure and associated
technology can encompass other embodiments not expressly shown
and/or described herein.
[0207] Throughout this disclosure, the singular terms "a," "an,"
and "the" include plural referents unless the context clearly
indicates otherwise. Similarly, unless the word "or" is expressly
limited to mean only a single item exclusive from the other items
in reference to a list of two or more items, then the use of "or"
in such a list is to be interpreted as including (a) any single
item in the list, (b) all of the items in the list, or (c) any
combination of the items in the list. Additionally, the terms
"comprising" and the like are used throughout this disclosure to
mean including at least the recited feature(s) such that any
greater number of the same feature(s) and/or one or more additional
types of features are not precluded. Directional terms, such as
"upper," "lower," "front," "back," "vertical," and "horizontal,"
may be used herein to express and clarify the relationship between
various elements. It should be understood that such terms do not
denote absolute orientation. Reference herein to "one embodiment,"
"an embodiment," or similar formulations means that a particular
feature, structure, operation, or characteristic described in
connection with the embodiment can be included in at least one
embodiment of the present technology. Thus, the appearances of such
phrases or formulations herein are not necessarily all referring to
the same embodiment. Furthermore, various particular features,
structures, operations, or characteristics may be combined in any
suitable manner in one or more embodiments.
* * * * *