U.S. patent application number 15/204349 was filed with the patent office on 2017-02-02 for intraluminal microneurography probe.
The applicant listed for this patent is NeuroMedic, Inc.. Invention is credited to Gregory G. Brucker, Harry A. Puryear, Jin Shimada.
Application Number | 20170027460 15/204349 |
Document ID | / |
Family ID | 57886741 |
Filed Date | 2017-02-02 |
United States Patent
Application |
20170027460 |
Kind Code |
A1 |
Shimada; Jin ; et
al. |
February 2, 2017 |
INTRALUMINAL MICRONEUROGRAPHY PROBE
Abstract
An intraluminal microneurography probe has a probe body that is
configured to be introduced into an artery near an organ of a body
without preventing the flow of blood through the artery. An
expandable sense electrode and an expandable stimulation electrode
are fixed to the probe body at one end of each electrode such that
movement of the other end toward the fixed end causes the sense
electrode to expand from the probe body toward a wall of the
artery. A ground electrode is configured to couple to the body, and
a plurality of electrical connections are operable to electrically
couple the electrodes to electrical circuitry. The sense electrode
is operable to measure sympathetic nerve activity in response to
excitation of the stimulation electrode. An ablation element is
located between the expandable sense electrode and expandable
stimulation electrode, and is operable to ablate nerves proximate
to the artery.
Inventors: |
Shimada; Jin; (White Bear
Lake, MN) ; Puryear; Harry A.; (Shoreview, MN)
; Brucker; Gregory G.; (Minneapolis, MN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
NeuroMedic, Inc. |
Minnetonka |
MN |
US |
|
|
Family ID: |
57886741 |
Appl. No.: |
15/204349 |
Filed: |
July 7, 2016 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
62198382 |
Jul 29, 2015 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/04001 20130101;
A61B 2018/00577 20130101; A61B 2018/1407 20130101; A61B 5/4035
20130101; A61B 5/201 20130101; A61B 2018/1861 20130101; A61B
2562/028 20130101; A61B 2018/00023 20130101; A61B 2018/00267
20130101; A61B 2018/00511 20130101; A61B 2018/126 20130101; A61B
2018/162 20130101; A61B 2562/0209 20130101; A61B 18/1815 20130101;
A61B 5/4836 20130101; A61B 5/6876 20130101; A61B 2018/1253
20130101; A61B 2018/00839 20130101; A61B 2562/043 20130101; A61B
18/1492 20130101; A61B 5/725 20130101; A61B 2018/1467 20130101;
A61B 2018/00434 20130101; A61B 2018/00404 20130101 |
International
Class: |
A61B 5/04 20060101
A61B005/04; A61B 5/00 20060101 A61B005/00; A61B 18/14 20060101
A61B018/14; A61B 5/20 20060101 A61B005/20 |
Claims
1. An intraluminal microneurography probe, comprising: a probe body
that is substantially cylindrical and having a diameter and a
length that is perpendicular to the diameter, the probe configured
to be introduced into an artery near an organ of a body without
preventing the flow of blood through the artery; an expandable
sense electrode, fixed to the probe body at one end of the sense
electrode and movable relative to the probe body at a second end of
the sense electrode such that movement of the movable end toward
the fixed end causes the sense electrode to expand from the probe
body toward a wall of the artery; an expandable stimulation
electrode, fixed to the probe body at one end of the stimulation
electrode and movable relative to the probe body at a second end of
the stimulation electrode such that movement of the movable end
toward the fixed end causes the sense electrode to expand from the
probe body toward a wall of the artery; a ground electrode
configured to couple to the body; a plurality of electrical
connections operable to electrically couple at least the expandable
sense electrode, expandable stimulation electrode, and ground
electrode to electrical circuitry.
2. The intraluminal microneurography probe of claim 1, wherein the
sense electrode wire is equal to or smaller than 10 thousandths of
an inch in a direction of nerve propagation.
3. The intraluminal microneurography probe of claim 1, wherein at
least one of the expandable sense electrode and the expandable
stimulation electrode comprises an expandable mesh.
4. The intraluminal microneurography probe of claim 1, wherein at
least one of the expandable sense electrode and the expandable
stimulation electrode comprises an expandable wire helix.
5. The intraluminal microneurography probe of claim 1, wherein the
diameter of the probe body is 2 mm or less.
6. The intraluminal microneurography probe of claim 1, wherein the
expandable sense electrode and the expandable stimulation electrode
have fixed points on the probe body that are between two and four
centimeters apart along the length of the probe body.
7. The intraluminal microneurography probe of claim 1, wherein the
ground electrode is configured on or near the probe body.
8. The intraluminal microneurography probe of claim 1, further
comprising a second ground electrode such that separate sense
ground and stimulation ground electrodes are provided.
9. The intraluminal microneurography probe of claim 1, wherein the
separate sense ground and stimulation ground electrodes are coupled
to one another via a low-pass filter.
10. The intraluminal microneurography probe of claim 1, further
comprising a sheath assembly operable to guide the probe into
position within the artery.
11. The intraluminal microneurography probe of claim 10, wherein
the ground electrode is coupled to the sheath.
12. The intraluminal microneurography probe of claim 11, further
comprising a second ground electrode couplable to the body such
that separate sense ground and stimulation ground electrodes are
provided
13. The intraluminal microneurography probe of claim 11, wherein
the ground electrode coupled to the sheath and the second ground
electrode couplable to the body are coupled to one another via a
low-pass filter.
14. The intraluminal microneurography probe of claim 1, further
comprising a neural ablation element attached to the probe
body.
15. The intraluminal microneurography probe of claim 14, wherein
the neural ablation element is attached to the probe body at a
location between the expandable sense electrode and the expandable
stimulation electrode.
16. A method of characterizing nerve activity associated with a
body organ, comprising: introduction of a probe into artery to a
location proximate to the body organ; expansion of an expandable
sense electrode and an expandable stimulation electrode comprising
a part of the probe to contact the artery wall while permitting
blood flow around the expanded sense and stimulation electrodes;
excitation of the stimulation electrode using an electricity source
coupled to the stimulation electrode; and measurement of
sympathetic nerve activity as a result of exciting the stimulation
electrode using the expanded sense electrode.
17. The method of characterizing nerve activity associated with a
body organ of claim 16, further comprising ablation of nerves in
the vicinity of the location proximate to the body organ.
18. The method of characterizing nerve activity associated with a
body organ of claim 17, where ablation is performed via an ablation
element comprising a part of the probe.
19. The method of characterizing nerve activity associated with a
body organ of claim 17, further comprising re-excitation of the
stimulation electrode using an electricity source coupled to the
stimulation electrode, and re-measurement of sympathetic nerve
activity as a result of exciting the stimulation electrode using
the expanded sense electrode to confirm the effects of the
ablation
20. The method of characterizing nerve activity associated with a
body organ of claim 16, wherein introduction of the probe into the
artery comprises introducing the probe into the artery via a
sheath.
Description
[0001] This application claims the benefit of U.S. Provisional
Application No. 62/192,340 filed Jul. 14, 2015, the contents of
which are herein incorporated by reference.
FIELD
[0002] The invention relates generally to neural measurement, and
more specifically to an intraluminal microneurography probe.
BACKGROUND
[0003] The human body's nervous system includes both the somatic
nervous system that provides sense of the environment (vision, skin
sensation, etc.) and regulation of the skeletal muscles, and is
largely under voluntary control, and the autonomic nervous system,
which serves mainly to regulate the activity of the internal organs
and adapt them to the body's current needs, and which is largely
not under voluntary control. The autonomic nervous system involves
both afferent or sensory nerve fibers that can mechanically and
chemically sense the state of an organ, and efferent fibers that
convey the central nervous system's response (sometimes called a
reflex arc) to the sensed state information. In some cases, the
somatic nervous system is also influenced, such as to cause
vomiting or coughing in response to a sensed condition.
[0004] Regulation of the human body's organs can therefore be
somewhat characterized and controlled by monitoring and affecting
the nerve reflex arc that causes organ activity. For example, the
renal nerves leading to the kindey can often cause a greater
reflexive reaction than desired, contributing significantly to
hypertension. Measurement of the nerve activity near the kidney,
and subsequent ablation of some (but not all) of the nerve can
therefore be used to control the nervous system's overstimulation
of the kindey, improving operation of the kidney and the body as a
whole.
[0005] Because proper operation of the nervous system is therefore
an important part of proper organ function, it is desired to be
able to monitor and change nervous system function in the human
body to characterize and correct nervous system regulation of
internal human organs.
SUMMARY
[0006] One example embodiment of the invention comprises an
intraluminal microneurography probe, having a probe body that is
substantially cylindrical and that is configured to be introduced
into an artery near an organ of a body without preventing the flow
of blood through the artery. An expandable sense electrode is fixed
to the probe body at one end of the sense electrode and is movable
relative to the probe body at a second end of the sense electrode
such that movement of the movable end toward the fixed end causes
the sense electrode to expand from the probe body toward a wall of
the artery, and an expandable stimulation electrode is fixed to the
probe body at one end of the stimulation electrode and movable
relative to the probe body at a second end of the stimulation
electrode such that movement of the movable end toward the fixed
end causes the sense electrode to expand from the probe body toward
a wall of the artery. A ground electrode configured to couple to
the body, and a plurality of electrical connections are operable to
electrically couple at least the expandable sense electrode,
expandable stimulation electrode, and ground electrode to
electrical circuitry.
[0007] In further examples, the sense electrode wire is equal to or
smaller than 10 thousandths of an inch in a direction of nerve
propagation, and at least one of the expandable sense electrode and
the expandable stimulation electrode comprises an expandable mesh
or an expandable wire helix. In another example, the diameter of
the probe body is 2 mm or less, such that blood flow is not blocked
by introduction of the probe into the artery.
[0008] In another example nerve activity associated with a body
organ is characterized by introduction of a probe into artery to a
location proximate to the body organ, and expansion of an
expandable sense electrode and an expandable stimulation electrode
comprising a part of the probe to contact the artery wall while
permitting blood flow around the expanded sense and stimulation
electrodes. An electricity source coupled to the stimulation
electrode is used to excite the stimulation electrode, and the
expanded sense electrode is used to measure sympathetic nerve
activity as a result of exciting the stimulation electrode.
[0009] In a further example, ablation of nerves in the vicinity of
the location proximate to the body organ is performed such as via
an ablation element comprising a part of the probe, and
re-excitation of the stimulation electrode using an electricity
source coupled to the stimulation electrode, and re-measurement of
sympathetic nerve activity as a result of exciting the stimulation
electrode using the expanded sense electrode are performed to
confirm the effects of the ablation
[0010] The details of one or more examples of the invention are set
forth in the accompanying drawings and the description below. Other
features and advantages will be apparent from the description and
drawings, and from the claims.
BRIEF DESCRIPTION OF THE FIGURES
[0011] FIG. 1 illustrates an intraluminal microneurography probe
having expandable helical wire electrodes, consistent with an
example.
[0012] FIG. 2 illustrates an intraluminal microneurography probe
having expandable wire mesh electrodes, consistent with an
example.
[0013] FIG. 3 shows introduction of an intraluminal
microneurography probe into an artery in a location near a kidney,
consistent with an example.
[0014] FIG. 4 shows an intraluminal microneurography probe and
sheath assembly coupled to associated instrumentation, consistent
with an example.
[0015] FIG. 5 shows spontaneous nerve activity, measured from the
wall of the renal artery of an explanted kidney, consistent with an
example.
[0016] FIG. 6 shows spontaneous nerve activity in the wall of the
renal artery of an explanted kidney using an intraluminal
microneurography probe, consistent with an example.
[0017] FIG. 7, shows a stimulus signal and the resulting measured
RSNA action potential, consistent with an example.
[0018] FIG. 8 shows destruction of the renal sympathetic nerves and
the resulting effects on RSNA signals measured as a result of an
applied stimulus signal, consistent with an example.
[0019] FIG. 9 is a flowchart illustrating a method of using an
intraluminal microneurography probe to treat a medical condition,
consistent with an example.
DETAILED DESCRIPTION
[0020] In the following detailed description of example
embodiments, reference is made to specific example embodiments by
way of drawings and illustrations. These examples are described in
sufficient detail to enable those skilled in the art to practice
what is described, and serve to illustrate how elements of these
examples may be applied to various purposes or embodiments. Other
embodiments exist, and logical, mechanical, electrical, and other
changes may be made. Features or limitations of various embodiments
described herein, however important to the example embodiments in
which they are incorporated, do not limit other embodiments, and
any reference to the elements, operation, and application of the
examples serve only to define these example embodiments. Features
or elements shown in various examples described herein can be
combined in ways other than shown in the examples, and any such
combination is explicitly contemplated to be within the scope of
the examples presented here. The following detailed description
does not, therefore, limit the scope of what is claimed.
[0021] Regulating operation of the nervous system to characterize
and improve organ function includes in some examples introduction
of a probe such as a needle, catheter, wire, or the like into the
body to a specified anatomical location, and partially destroying
or ablating nerves using the probe to destroy nerve tissue in the
region near the probe. By reducing nerve function in the selected
location, an abnormally functioning physiological process can often
be regulated back into a normal range.
[0022] Unfortunately, it is typically very difficult to estimate
the degree to which nerve activity has been reduced, which makes it
difficult to perform a procedure where it is desired to ablate
some, but not all, nerves to bring the nervous system response back
into a desired range without destroying the nervous system response
entirely.
[0023] One such example is renal nerve ablation to relieve
hypertension. Various studies have confirmed that improper renal
sympathetic nerve function has been associated with hypertension,
and that ablation of the nerve can improve renal function and
reduce hypertension. In a typical procedure, a catheter is
introduced into a hypertensive patient's arterial vascular system
and advanced into the renal artery. Renal nerves located in the
arterial wall and in regions adjacent to the artery are ablated by
destructive means such as radio frequency waves, ultrasound, laser
or chemical agents to limit the renal sympathetic nerve activity,
thereby reducing hypertension in the patient.
[0024] Unfortunately, renal nerve ablation procedures are often
ineffective, such as due to either insufficiently ablating the
nerve or destroying more nerve tissue than is desired. Clinicians
often estimate based on provided guideline estimates or past
experience the degree to which application of a particular ablative
method will reduce nerve activity, and it can take a significant
period of recovery time (3-12 months) before the effects of the
ablation procedure are fully known.
[0025] Some attempt has been made to monitor nerve activity in such
procedures by inserting very small electrodes into or adjacent to
the nerve body, which are then used to electrically monitor the
nerve activity. Such microneurography practices are not practical
in the case of renal ablation because the renal artery and nerves
are located within the abdomen and cannot be readily accessed,
making monitoring and characterization of nerve activity in a renal
nerve ablation procedure a challenge.
[0026] Prior methods such as inserting electrodes into the arteries
of a patient's heart and analyzing received electrical signals are
not readily adaptable to renal procedures, as arteries in the heart
are generally large and more readily accommodate probes for
performing such measurements. Further, the cardiac electrical
signals emitted from the heart are generally large and slow-moving
relative to electrical signals near the renal arteries, which tend
to be smaller in size and produce smaller signals that propagate
more quickly through the nerves. As such, intravascular techniques
used in heart measurements are readily adaptable to similar renal
processes.
[0027] Because nerve activity during organ procedures such as renal
nerve ablation cannot be readily measured, it is also difficult to
ensure that an ablation probe is located at the most appropriate
sites along the renal artery, or to measure the efficiency of the
nerve ablation process in a particular patient.
[0028] Some examples presented herein therefore provide an improved
probe and method for characterizing nerve activity near an organ
such as a kidney, including electrodes configured specifically to
measure nerve activity in an environment different from the heart
while permitting blood flow around the probe. In a more detailed
example, the probe includes a sense electrode and a stimulation
electrode that are expandable from a body of the probe, which can
be introduced via a sheath. The sheath in a further embodiment
comprises one or more electrodes, such as one or more sense
electrode reference or ground electrodes.
[0029] FIG. 1 illustrates an example of such a probe. Here, a probe
assembly is shown generally at 100, including probe body 102, and
first and second helical electrodes 104 and 106. Each of the
helical electrodes is attached to the probe body at one end, shown
here as an attachment point 108, such as an epoxy bead or other
suitable attachment mechanism. The opposite end of each of the
helical electrodes is constrained in the example shown, such as by
emerging through a hole in the probe as shown by helical electrode
106, and extends from the left end of the probe assembly to connect
to electronic instrumentation to perform various functions. The
configuration of the helical electrode wires is such that the wires
will expand about the axis of the probe body 102 when the wire of
each helical electrode is forced toward the attachment points 108,
causing the wire to form a circular shape having a diameter
substantially larger than the helical electrode wires in the
collapsed position, as shown at 100.
[0030] The probe assembly is shown again at 110, here with the
helical electrode wires 104 and 106 forced toward the attachment
points 108, causing the wire to expand away from the probe body
102. This helical expansion allows the helical electrodes to expand
in an environment such as an artery such as to contact the artery
walls while allowing blood to flow around the probe body 102 and
past the helical electrodes 104 and 106.
[0031] Another example of a probe configured to characterize nerve
activity near an organ such as a kidney while permitting blood flow
around the probe is shown in FIG. 2. Here, a probe body is shown at
202, having mesh electrodes 204 and 206 affixed thereto at
attachment points 208. The mesh electrodes are substantially
similar to the helical wire electrodes of FIG. 1, except that
several such electrodes are interwoven to form a mesh that is
closely wrapped around the probe body 202. In this example, each
mesh electrode also has a sliding collar element 209 located at the
end of the mesh electrode opposite attachment point 208.
[0032] This sliding collar 209 when moved toward the attachment
point 208 causes the mesh to expand around the probe body 202, as
shown generally at 210. Here, the expanded mesh electrodes 204 and
206 are configured to provide electrical contact, such as with an
artery wall, in a diameter significantly larger than the diameter
of the probe body 202. This enables insertion of the probe body
into an artery, and expansion of the electrodes 204 and 206 to
contact the artery walls, without blocking blood flow through the
artery. Although the examples of FIGS. 1 and 2 show two probe
configurations that can achieve such functions, probe
configurations other than those shown here may also be configured
to achieve these or similar functions.
[0033] FIG. 3 illustrates one example of use of such a probe, in
which a probe 302 such as that shown in FIG. 1 or FIG. 2 is
introduced into a blood vessel, such as an artery 304, in a
location near a body organ such as kidney 306. The probe is
introduced via a sheath in some examples, such as where a sheath is
advanced to the intended probe location in the artery, and then
withdrawn sufficiently to expose the probe 302 to the artery 304.
The probe 302 here comprises a stimulation electrode such as
electrodes 104 and 204 of FIGS. 1 and 2, and a sense electrode such
as electrodes 106 and 206 of the same Figures.
[0034] When deployed, the electrodes are expanded as shown at 308,
such that they are near or touch the walls of the artery 304. The
electrodes are thereby located nearer the nerve bundle 310
connecting the kidney to the central nervous system, as the nerve
bundle tends to approximately follow the artery leading to most
body organs. As shown at 310, the nerve bundle tends to follow the
artery more closely at the end of the artery closer to the kidney,
while spreading somewhat as the artery expands away from the
kidney. As a result, it is desired in some examples that the probe
is small enough to introduce relatively near the kidney or other
organ, as nerve proximity to the artery is likely to be higher
nearer the organ.
[0035] When in place, a practitioner can use instrumentation
coupled to the sense electrode and stimulation electrode to
stimulate the nerve, and monitor for nerve response signals used to
characterize the nervous system response to certain stimulus. In a
further example, an ablation element 308 is configured to ablate
nerve tissue, such as by using radio frequency, ultrasound, or
other energy, such that the probe can actively stimulate the nerve
and sense resulting neural signals in between applications of
energy via the ablation element 308, enabling more accurate control
of the degree and effects of nerve ablation. In other examples, a
probe 302 lacking an ablation element can be remove via the sheath,
and an ablation probe inserted, with the ablation probe removed and
the probe 302 reinserted to verify and characterize the effects of
the ablation probe.
[0036] FIG. 4 shows an intraluminal microneurography probe and
sheath assembly coupled to associated instrumentation, consistent
with an example. Here, a probe body 402 has an expandable sense
electrode 404 and an expandable stimulation electrode 406, couple
via wires to instrumentation. A sheath 408 is used to introduce the
probe into an artery or other biological lumen or suitable
location, and to carry instrumentation wires and mechanical
connections used to manipulate the expandable electrodes. The
electrodes are not shown here running through the sheath, but are
instead shown as schematic links between the electrodes and various
instrumentation circuitry for clarity.
[0037] In this example, the expandable sense electrode 404 is
coupled to a sense circuit, such as a differential amplifier as
shown at 410, with the other input to the sense amplifier circuit
coupled to a ground electrode such as local ground electrode 412
coupled to the sheath 408. In another example, local ground
electrode is located elsewhere, such as on the probe body 404. The
expandable stimulation electrode 406 is similarly coupled to a
stimulation circuit 414 that is operable to provide a stimulation
voltage or current signal of a desired pulse shape, intensity, and
duration to the expandable stimulation electrode 406, with
reference to body ground. Body ground is established in this
example by a body ground electrode 416, which is here also shown as
coupled to the sheath 408, but which in other embodiments will take
other forms such as an electrode coupled to the body's skin. Here,
the body ground electrode 416 is further coupled to the local
ground electrode 412 by use of a low-pass filter, having a
frequency response or time constant selected such that the local
ground electrode does not drift significantly from the body ground
level but retains the ability to accurately detect and characterize
local nerve impulses.
[0038] The electrodes in this example comprise electrical wires
that are significantly smaller than are used in other applications
such as cardiac probes, in part because the pulse duration in the
nerve bundle leading to most body organs is typically much shorter
than a cardiac muscle excitation signal. In one embodiment, the
sense electrode 404 therefore comprises a wire or mesh of wires
having a diameter of 8-10 thousandths of an inch, while in other
examples the wire diameter is 5-10 thousandths, 5-15 thousandths,
or any size under 15, 10, 8, or 5 thousandths of an inch. The sense
electrode is thereby configured to accurately detect a typical
nerve action potential of 2 milliseconds traveling at a meter per
second without smearing or distorting the measured pulse due to an
overly large electrode.
[0039] The stimulation electrode in various examples comprises a
wire or mesh of wires having any of the above sizes, but in another
example, it is desired that the stimulation electrode 406 be
substantially larger than the sense electrode 404 to avoid
hyperpolarization of the nerve in the region of the electrode
during stimulation.
[0040] Wire size of electrodes such as the sense electrode 404 is
selected in further examples based on a typical nerve conduction
velocity range of 0.4-2 meters/second, with nerve impulses ranging
from 1-3 milliseconds. Also, the sense electrode 404 and
stimulation electrode 406 are desirably placed a sufficient
distance apart, such as 3 centimeters, to accurately detect a
typical nerve action potential of 2 milliseconds without
interference from the stimulation electrode.
[0041] Because the size of organ arteries such as the renal artery
are typically in the range of 5 millimeters in diameter, it is
desired to have a probe body that is a fraction of this size, such
as having a diameter of 2.5 mm, 2 mm, 1 mm, or similar. This
enables introduction of the probe without interfering with blood
flow through the artery, such that the expandable electrodes can
still expand to the artery walls without further significantly
impeding blood flow.
[0042] An intraluminal microneurographic probe such as those shown
in FIGS. 1-4 can therefore be introduced into an artery via a
sheath, and used to monitor nerve activity during normal operation
of an organ. This enables characterization of nerve activity in the
organ, such as to diagnose or treat a variety of conditions. In one
such example, a probe is used for characterization of overactive
nerves reaching the kidney in patients suffering from hypertension,
and to monitor ablation of the nerves to a point where nerve
activity is in the desired range as measured using the probe. In
other examples, the probe may be used while other actions are
performed, such as to monitor nerve activity to a patient's
prostate while surgery or other methods remove material to treat
prostate cancer or enlarged prostate problems. Because it is
desirable that significant nerve connection to the prostate be
preserved during such procedures, a probe such as those presented
here can be used to minimize the chances of nerve damage that may
affect normal function of the prostate.
[0043] A probe such as those shown here can also be used to
diagnose various organ dysfunctions, such as where an organ
overreacts to nerve impulses or overstimulates the nerve in
response to organ activity. The probe is here described in some
examples as an intraluminal probe, meaning the probe may be
introduced into various lumina or pathways in the body, such as
arteries, veins, the gastrointestinal tract, pathways of bronchii
in the lungs, pathways of the genitourinary tract, and other such
pathways. The probe is neurographic in the sense that it enables
characterization, such as measurement, recording, and visualization
of neurologic activity in the vicinity of the probe. Because the
autonomic nervous system regulates a wide variety of functions
within the body, including circulation, digestion, metabolism,
respiration, reproduction, etc. by a network of parasympathetic and
sympathetic nerves that typically accompany the blood vessels
supplying blood to the organs they regulate, an intraluminal
neurographic probe such as those described here can be used to
measure or characterize the regulation of many of these functions
by introducing the probe into the blood vessels near the organ of
interest.
[0044] Although the example of FIG. 3 illustrates ablation of
nerves near the kidney to regulate kidney function in treating
hypertension, nerves regulating liver function accompany the
hepatic artery and the portal vein, nerves regulating the stomach
accompany the gastroduodenal arteries, nerves from the superior
mesenteric plexus accompany the superior mesenteric artery and
branch to the pancreas, small intestine and large intestine, and
nerves of the inferior mesenteric plexus accompany the inferior
mesenteric artery and branch to the large intestine, colon and
rectum. These examples illustrate other organs that can be
characterized and regulated using probes and techniques such as
those described herein.
[0045] In treating kidney function, it is significant that renal
sympathetic nerves have been identified as a major contributor to
the complex pathophysiology of hypertension. Patients with
hypertension generally have increased sympathetic drive to the
kidneys, as evidenced by elevated rates of the renal norepinephrine
"spillover." It is therefore believed that ablating renal
sympathetic nerve function with sufficient energy will cause a
reduction in both systolic and diastolic blood pressure, relieving
hypertension in the patient.
[0046] Studies have shown that most nerves surrounding the renal
arteries are within two millimeters of the renal artery, with
nerves clustered more closely around the artery near the kidney,
making measurement and treatment of the nerves from the renal
artery practical. But, as complete destruction or ablation of the
nerves is likely not desirable, monitoring nerve activity during or
between nerve ablations, such as via the probes described herein,
is an important tool in characterizing and regulating the degree to
which nerve activity has been reduced. Before introduction of
probes such as those described here, clinicians were unable to
readily determine extent of renal sympathetic nerve modification
during a procedure in a clinically relevant timeframe, and could
not measure durability of nerve damage during follow-up period
after denervation. Now, with probes such as those described herein
available, a clinician can take such measurements, and can to
assess health of renal sympathetic nerves pre-procedurally to
select or screen patients for denervation.
[0047] In operation, a clinician can measure nerve activity such as
renal sympathetic nerve activity (RSNA) by emitting an electrical
pulse through stimulation electrodes in the probe, and recording
propagation along renal sympathetic nerve fibers using the sense
electrode or electrodes on the probe. The clinician can then
compare RSNA pre- and post-denervation to determine the degree of
nerve ablation incurred, thereby more accurately achieving the
desired degree of nerve ablation during treatment of the patient.
More specifically, a clinician can apply an electrical stimulus to
a site in the proximal renal artery, and then monitor or record the
nerve activity between the stimulus site and the kidney, thereby
measuring the resultant downstream action potential in the nerve.
Nerve ablation is then performed, and the stimulus and measurement
of the nerve is repeated to verify a reduced or eliminated evoked
potential detected in the nerve as a result of stimulation via the
probe's electrodes.
[0048] The probe system described in the examples here can
therefore provide real-time feedback on functionality of renal
sympathetic nerves, providing integrated evaluation of all nerve
fibers surrounding a renal artery, at the artery proximal, distal,
and renal branch locations. The probe is easily deployed via
catheter-based delivery, and can be used as a standalone product or
integrated with an ablation element. The probe system's low
hardware and software costs and easy learning curve for clinical
users make the probe system well-adapted for widespread adoption
for treatment of nerve conditions such as those described
herein.
[0049] A variety of experiments have been conducted to verify
operation of probes such as those described herein, including using
an isolated canine/porcine kidney and the associated vasculature to
conduct certain tests. In one such test, probes such as those of
FIGS. 1-4 were used to verify renal nerve health by measuring
spontaneous renal sympathetic nerve activity (RSNA) using
intraluminal microneurography, demonstrating that such probes cause
effective stimulation and recording of RSNA. In the tests,
stimulus-elicited response established a baseline recording of
RSNA, and the circumferential section of renal nerve fibers were
damaged using a scalpel. Remeasuring the stimulus-elicited response
and comparing the response to the established baseline recording of
RSNA confirmed that spontaneous sympathetic renal nerve activity
had been reduced.
[0050] FIG. 5 shows spontaneous nerve activity, measured from the
wall of the renal artery of an explanted kidney. Here, the
measurements are taken using needles placed in the wall of the
renal artery, using relatively invasive microneurography
techniques.
[0051] FIG. 6 shows spontaneous nerve activity in the wall of the
renal artery of an explanted kidney, using an intraluminal
microneurography probe. Here, the peak signal levels are somewhat
reduced relative to the method of FIG. 5, but accurate detection,
measurement, and recording of spontaneous RSNA signals is shown to
be achieved.
[0052] In FIG. 7, a stimulus signal (top) and the resulting
measured RSNA action potential are shown. Here, the renal nerve
RSNA action potential is measured using needles in the artery wall,
using a stimulus time of approximately 1.3 milliseconds, configured
to avoid overlapping the stimulus and response signals based on the
expected conduction velocity and the selected stimulus and sense
electrode spacing.
[0053] Subsequent testing on live animals also proved successful,
with a series of experiments conducted in a live rat model to
confirm detection of renal sympathetic nerve activity (RSNA) in a
living animal with competing signals from cardiac electrical
activity and respiratory movement. Excellent results were achieve
using probes having configurations such as those described herein,
based on an experimental procedure in which an evoked RSNA baseline
was determined in the intact renal artery, and RSNA was measured as
the renal artery was transected.
[0054] Destruction of the renal sympathetic nerves, and the
resulting effects on RSNA signals measured as a result of an
applied stimulus signal, are shown in FIG. 8. Here, ten sets of
data are overlaid to generate a graph representative of typical
levels and distribution of RSNA response to a stimulus signal as
varying degrees of arterial transection. At 802, the evoked RSNA
baseline measurements taken prior to cutting across the artery are
taken as a reference. At 804, the artery is 50% transected,
resulting in significant reduction in observed RSNA response, and
at 806, the artery is 100% transected, and little to no RSNA
response is observed. In this example, transection of the renal
arteries was used to destroy renal neural pathways because rat
renal arteries are too small for effective radio frequency
ablation.
[0055] FIG. 9 is a flowchart illustrating a method of using an
intraluminal microneurography probe to treat a medical condition,
consistent with an example. As shown generally at 900, a method of
treating a medical condition involves using probe to excite and
measure nerve activity near an organ, and selectively ablating
nerve tissue near the probe until the desired nerve activity in
response to the excitation is observed.
[0056] A sheath carrying the probe into the artery is inserted at
902, and is advanced to a location in the artery near a body organ
that is the subject of the medical condition and treatment, such as
treating a kidney's neural sympathetic response to treat
hypertension. The sheath is withdrawn slightly at 904, exposing at
least part of the probe including an expandable sense electrode and
an expandable stimulation electrode to the artery. At 906, the
expandable stimulation and sense electrodes are expanded, such that
the electrodes contact the arterial wall while permitting blood
flow around the probe and the electrodes. At this point, the probe
is properly deployed and ready to perform measurement.
[0057] The expandable stimulation electrode is excited at 908,
inducing an electrical signal into the nerves adjacent to the
arterial wall. The nerves propagate the signal from the stimulation
electrode, which can be observed at 910 as sympathetic nerve
activity as a result of exciting the stimulation electrode. The
observed sympathetic nerve activity can then be measured,
characterized, stored, viewed, etc., to determine whether the
sympathetic nerve activity exceeds a desired level at 912. If a
desired level of sympathetic nerve activity is exceeded, nerves
proximate the probe are ablated at 914, such as using an ablation
element comprising a part of the probe located between the sense
electrode and the stimulation electrode. Steps 908-912 are then
repeated, until the sympathetic nerve activity is determined not to
exceed the desired level at 912. At that point, the measurement and
nerve ablation is complete, and the probe and sheath can be
withdrawn at 916.
[0058] Although the examples presented here primarily illustrate
measurement of sympathetic nerve activity using the probe systems
described, probe system such as those illustrated here can also be
used to monitor organ activity, pain, or other nervous system
indicia. For example, pain can be monitored during surgery in some
applications, or nerve activity can be measured while externally
stimulating an organ.
[0059] Although specific embodiments have been illustrated and
described herein, any arrangement that achieve the same purpose,
structure, or function may be substituted for the specific
embodiments shown. This application is intended to cover any
adaptations or variations of the example embodiments of the
invention described herein. These and other embodiments are within
the scope of the following claims and their equivalents.
* * * * *