U.S. patent application number 14/573291 was filed with the patent office on 2015-05-14 for devices and methods for photodynamically modulating neural function in a human.
The applicant listed for this patent is Medtronic Ardian Luxembourg S.a.r.l.. Invention is credited to Ayala Hezi-Yamit, Robert J. Melder, Christopher W. Storment, Carol M. Sullivan.
Application Number | 20150133904 14/573291 |
Document ID | / |
Family ID | 48803605 |
Filed Date | 2015-05-14 |
United States Patent
Application |
20150133904 |
Kind Code |
A1 |
Melder; Robert J. ; et
al. |
May 14, 2015 |
Devices and Methods for Photodynamically Modulating Neural Function
in a Human
Abstract
Devices and methods for therapeutic photodynamic modulation of
neural function in a human. One embodiment of a method in
accordance with the technology includes administering a
photosensitizer to a human, wherein the photosensitizer
preferentially accumulates at nerves proximate a blood vessel
compared to non-neural tissue of the blood vessel. The method can
further include irradiating the photosensitizer using a radiation
emitter positioned within the human, wherein the radiation has a
wavelength that causes the photosensitizer to react and alter at
least a portion of the nerves thereby providing a therapeutic
reduction in sympathetic neural activity. Several embodiments of
the technology are useful for disrupting renal nerves, such as
renal denervation, for treating hypertension, diabetes, congestive
heart failure, and other indications.
Inventors: |
Melder; Robert J.; (Santa
Rosa, CA) ; Hezi-Yamit; Ayala; (Windsor, CA) ;
Storment; Christopher W.; (Sonoma, CA) ; Sullivan;
Carol M.; (Petaluma, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Medtronic Ardian Luxembourg S.a.r.l. |
Luxembourg |
|
LU |
|
|
Family ID: |
48803605 |
Appl. No.: |
14/573291 |
Filed: |
December 17, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
13826604 |
Mar 14, 2013 |
8951296 |
|
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14573291 |
|
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61666687 |
Jun 29, 2012 |
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Current U.S.
Class: |
606/14 ;
607/92 |
Current CPC
Class: |
A61N 5/062 20130101;
A61N 2005/0666 20130101; A61B 2018/00434 20130101; A61N 2005/063
20130101; A61N 2005/0651 20130101; A61N 5/0601 20130101; A61N
2005/0652 20130101; A61B 2018/0022 20130101; A61B 18/18 20130101;
A61N 2005/0602 20130101; A61N 2005/0661 20130101; A61B 2018/00791
20130101 |
Class at
Publication: |
606/14 ;
607/92 |
International
Class: |
A61B 18/18 20060101
A61B018/18; A61N 5/06 20060101 A61N005/06 |
Claims
1-34. (canceled)
35. A system for performing photodynamic therapy, comprising: a
treatment device having an elongated shaft and a radiation unit at
a distal portion of the elongated shaft, wherein the radiation unit
has a positioning member and at least one radiation emitter, and
wherein the positioning member is configured to have a low-profile
delivery state for intravascular passage to a target site and a
deployed state in which the positioning member is configured to
contact a wall of a body lumen such that the radiation emitter is
stabilized at a desired location relative to target tissue; and a
controller configured to be coupled to the treatment device,
wherein the controller is adapted to cause radiation at a
wavelength of 351 nm-355 nm to be delivered from the radiation unit
to deliver 0.5-500 J/cm.sup.2 of radiation to a target.
36. The system of claim 35, wherein the controller has a radiation
source and the radiation emitter of the radiation unit comprises an
optic element configured to distributed the radiation to the target
tissue, and wherein the system further comprises a light guide
coupled to the controller and the optic element to transmit the
radiation from the controller to the optic element.
37. The system of claim 35, wherein the controller has a power
source and the radiation emitter of the radiation unit comprises a
radiation generator coupled to the positioning member, and wherein
the system further comprises an electrical lead electrically
coupled to the power source and the radiation generator.
38. The system of claim 37, wherein the radiation generator
comprises a light emitting diode.
39. The system of claim 37, wherein the radiation generator
comprise an array of light emitting diodes.
40. A device for therapeutically modulating sympathetic neural
system activity, comprising: an elongated shaft configured to pass
through vascular passages of a human; a balloon at a distal portion
of the elongated shaft, the balloon having a wall configured to
contact an inner wall of a blood vessel and an exterior channel
through which blood can flow when inflated to a deployed state; and
a radiation element at the balloon configured to deliver radiation
to perivascular nerves along the blood vessel.
Description
CROSS-REFERENCE TO RELATED APPLICATION(S)
[0001] The present application claims priority to U.S. Provisional
Patent Application No. 61/666,687, filed Jun. 29, 2012, entitled
"DEVICE AND METHOD FOR VASCULAR DELIVERY OF PHOTODYNAMIC THERAPY
FOR MODULATING NEURAL FUNCTION," which is incorporated herein in
its entirety by reference.
TECHNICAL FIELD
[0002] The present technology relates to modulation of neural
function, such as localized tissue denervation, using photodynamic
methods and devices.
BACKGROUND
[0003] The sympathetic nervous system (SNS) is a primarily
involuntary control system typically associated with stress
responses. SNS tissue fibers are present in almost every organ
system of the human body and can affect characteristics such as
pupil diameter, gut motility, and urinary output. Such regulation
can have adaptive utility in maintaining homeostasis or preparing
the body for rapid response to environmental factors. Chronic
activation of the SNS, however, is a common maladaptive response
that can drive the progression of many disease states. Excessive
activation of the renal SNS in particular has been identified
experimentally and in humans as a likely contributor to the complex
pathophysiology of hypertension, volume overload states (such as
heart failure), and progressive renal disease. For example,
radiotracer dilution has demonstrated increased renal
norepinephrine (NE) spillover rates in patients with essential
hypertension.
[0004] Cardio-renal sympathetic nerve hyperactivity can be
particularly pronounced in patients with heart failure. For
example, an exaggerated NE overflow from the heart and kidneys is
often found in these patients. Heightened SNS activation commonly
characterizes both chronic and end stage renal disease. In patients
with end stage renal disease, NE plasma levels above the median
have been demonstrated to be predictive of cardiovascular diseases
and several causes of death. This is also true for patients
suffering from diabetic or contrast nephropathy. Evidence suggests
that sensory afferent signals originating from diseased kidneys are
major contributors to initiating and sustaining elevated central
sympathetic outflow.
[0005] Sympathetic nerves innervating the kidneys terminate in the
blood vessels, the juxtaglomerular apparatus, and the renal
tubules. Stimulation of the renal sympathetic nerves can cause
increased renin release, increased sodium (Na.sup.+) reabsorption,
and a reduction of renal blood flow. These neural regulation
components of renal function are considerably stimulated in disease
states characterized by heightened sympathetic tone and likely
contribute to increased blood pressure in hypertensive patients.
The reduction of renal blood flow and glomerular filtration rate
that result from renal sympathetic efferent stimulation are likely
a cornerstone of the loss of renal function in cardio-renal
syndrome (i.e., renal dysfunction as a progressive complication of
chronic heart failure). Pharmacologic strategies to thwart the
consequences of renal efferent sympathetic stimulation include
centrally acting sympatholytic drugs, beta blockers (intended to
reduce renin release), angiotensin converting enzyme inhibitors and
receptor blockers (intended to block the action of angiotensin II
and aldosterone activation consequent to renin release), and
diuretics (intended to counter the renal sympathetic mediated
sodium and water retention). These pharmacologic strategies,
however, have significant limitations including limited efficacy,
compliance issues, side effects, and others. Recently,
intravascular devices that reduce sympathetic nerve activity by
applying an energy field to a target site in the renal artery have
been shown to reduce blood pressure in patients with
treatment-resistant hypertension (e.g., radiofrequency, cryogenic
or ultrasound ablation of renal nerves).
[0006] These devices seek to at least partially disrupt neural
function of nerves located in adventitial tissue around the renal
artery to achieve a therapeutic reduction in systemic blood
pressure. Each of these approaches damages or destroys the neural
tissue in the outer layers around the artery, and thus they also
affect the intimal, medial, and adventitial layers of the artery to
varying extents since the energy or temperature gradient must first
transverse the non-neural tissues to reach the intended target.
BRIEF DESCRIPTION OF THE DRAWINGS
[0007] 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.
[0008] FIG. 1 is a partially cross-sectional anatomical front view
illustrating several embodiments of a method for a therapeutic
neural modulation in a human in accordance with the present
technology.
[0009] FIG. 2 is a schematic cross-sectional view of a distal
portion of a treatment device at a target site in a blood vessel in
accordance with the present technology.
[0010] FIG. 3A is a schematic cross-sectional view of a distal
portion of a treatment device in accordance with the present
technology, and FIG. 3B is a cross-sectional view of the treatment
device taken along line B-B of FIG. 3A.
[0011] FIG. 4 is a partial cross-sectional view of a distal portion
of a treatment device for therapeutic neural modulation in
accordance with an embodiment of the present technology.
[0012] FIG. 5 is a partial cross-sectional view of a distal portion
of a treatment device for therapeutic neural modulation in
accordance with an embodiment of the present technology.
[0013] FIG. 6 is a partial cross-sectional view of a distal portion
of a treatment device for therapeutic neural modulation in
accordance with an embodiment of the present technology.
[0014] FIG. 7 is a partial cross-sectional view of a distal portion
of a treatment device for therapeutic neural modulation in
accordance with an embodiment of the present technology.
[0015] FIG. 8 is a partial cross-sectional view of a distal portion
of a treatment device for therapeutic neural modulation in
accordance with an embodiment of the present technology.
[0016] FIG. 9 is an isometric view having a cut-away portion
showing a distal portion of a treatment device for therapeutic
neuromodulation in accordance with an embodiment of the present
technology.
[0017] FIG. 10 is an isometric view further illustrating an
embodiment of operating the radiation unit.
[0018] FIG. 11 is schematic view of a system for operating
treatment devices for therapeutic neural modulation in accordance
with an embodiment of the present technology.
[0019] FIGS. 12-14 are charts showing the effects of UVA radiation
and/or oxytetracycline on differentiated PC12 cells from test
data.
DETAILED DESCRIPTION
[0020] Specific details of several embodiments of the technology
are described below with reference to FIGS. 1-14. Although many of
the embodiments are described below with respect to systems,
devices, and methods for renal neuromodulation using photodynamic
therapies, other applications and other embodiments in addition to
those described herein are within the scope of the technology.
Additionally, several other embodiments of the technology can have
different configurations, components, or procedures than those
described herein. A person of ordinary skill in the art, therefore,
will accordingly understand that the technology can have other
embodiments with additional elements, or the technology can have
other embodiments without several of the features shown and
described below with reference to FIGS. 1-14.
[0021] As used herein, the terms "distal" and "proximal" define a
position or direction with respect to the treating clinician or
clinician's control device (e.g., a handle assembly). "Distal" or
"distally" can refer to a position distant from or in a direction
away from the clinician or clinician's control device. "Proximal"
and "proximally" can refer to a position near or in a direction
toward the clinician or clinician's control device.
[0022] Renal neuromodulation is the partial or complete
incapacitation or other effective disruption of nerves innervating
the kidneys (e.g., rendering neural fibers inert or inactive or
otherwise completely or partially reduced in function). For
example, renal neuromodulation can include inhibiting, reducing,
disrupting, and/or blocking neural communication along neural
fibers innervating the kidneys (i.e., efferent and/or afferent
nerve fibers). Such incapacitation can be long-term (e.g.,
permanent or for periods of months, years, or decades) or
short-term (e.g., for periods of minutes, hours, days, or weeks).
Renal neuromodulation is expected to efficaciously treat several
clinical conditions characterized by increased overall sympathetic
activity, and, in particular, conditions associated with central
sympathetic overstimulation such as hypertension, heart failure,
acute myocardial infarction, metabolic syndrome, insulin
resistance, diabetes, left ventricular hypertrophy, chronic and end
stage renal disease, inappropriate fluid retention in heart
failure, cardio-renal syndrome, osteoporosis and sudden death,
among others. The reduction of afferent neural signals typically
contributes to the systemic reduction of sympathetic tone/drive,
and renal neuromodulation is expected to be useful in treating
several conditions associated with systemic sympathetic over
activity or hyperactivity. Renal neuromodulation can potentially
benefit a variety of organs and body structures innervated by
sympathetic nerves. For example, a reduction in central sympathetic
drive may reduce insulin resistance that afflicts patients with
metabolic syndrome and Type II diabetics.
[0023] Several embodiments of the present technology selectively
disrupt, and in many instances destroy, perivascular nerves without
adversely impairing the function of the non-neural tissues of the
blood vessel (e.g., intimal, medial and adventitial tissues of the
blood vessel). For example, several embodiments of methods for
therapeutic neural modulation in a human can include administering
a photosensitizer to a human that preferentially accumulates at
selected nerves compared to other tissues proximate the selected
nerves. For example, more of the photosensitizer can accumulate in
perivascular nerves around a blood vessel than in the non-neural
tissues of the blood vessel. The mechanisms for preferentially
accumulating the photosensitizer at the nerves can include faster
uptake by the nerves, longer residual times at the nerves, or a
combination of both. After a desired dosage of the photosensitizer
has accumulated at the nerves, the photosensitizer is irradiated
using a treatment device positioned within the human. The treatment
device delivers radiation to the target nerves at a wavelength that
causes the photosensitizer to react such that it damages or
disrupts the nerves. For example, the photosensitizer can become
toxic upon exposure to the radiation. Because the photosensitizer
preferentially accumulates at the nerves and not the other tissue
proximate the nerves, the toxicity and corresponding damage is
localized primarily at the nerves. Several embodiments of the
present technology are expected to be particularly useful for
denervation of perivascular nerves while protecting the non-neural
tissue of the blood vessel.
Selected Embodiments of Photodynamic Neuromodulation Methods and
Devices
[0024] FIG. 1 is a partially cross-sectional anatomical front view
illustrating several embodiments of methods for therapeutic neural
modulation in a human (H). An embodiment includes providing a
photosensitizer to neural tissue associated with sympathetic neural
activity. Several embodiments of the methods include providing the
photosensitizer to perivascular nerves, but other embodiments
include providing the photosensitizer to nerve ganglia, peripheral
nerves, and spinal nerves. The photosensitizer, for example, can be
administered either orally or by injecting the photosensitizer into
the human (H). For example, the photosensitizer can be injected
directly into the vasculature for systemic distribution, or the
photosensitizer can be injected into tissue proximate the target
nerves using appropriately sized needles for localized application.
In other embodiments, the photosensitizer can be delivered from
within the body lumen using an intravascular device. In any of
these embodiments, the photosensitizer is selected to
preferentially accumulate at the nerves as described in more detail
below.
[0025] FIG. 1 further illustrates delivering a treatment device 100
having a shaft 110 and a radiation unit 120 at a distal end of the
shaft 110 positioned within the vasculature of the patient.
Intravascular delivery of the radiation unit 120 can include
percutaneously inserting a guide wire (not shown) within the
vasculature at an access site (e.g., the femoral, brachial, radial,
or axillary artery). The shaft 110 and the radiation unit 120 are
moved along the guide wire in a low-profile delivery state until at
least a portion of the radiation unit 120 reaches a desired
treatment location. The shaft 110 and the radiation unit 120 can
include a guide wire lumen configured to receive a guide wire in an
over-the-wire or rapid exchange configuration. As illustrated, a
section of the proximal portion of a shaft 110 can be
extracorporeally positioned and manipulated by an operator via an
actuator 130 to advance the shaft 110 and radiation unit 120 along
an intravascular path (P) and remotely manipulate a distal portion
of the shaft 110.
[0026] The positioning and manipulation of the radiation unit 120
can be carried out using computed tomography (CT), fluoroscopy,
intravascular ultrasound (IVUS), optical coherence tomography
(OCT), intercardiac echocardiography (ICE), combinations thereof,
or other suitable guidance modalities. For example, a fluoroscopy
system including a flat-panel detector, x-ray or c-arm can rotated
to accurately visualize and identify the target treatment site.
Other embodiments can include locating the treatment site using
IVUS, OCT and other suitable imaging mapping modalities that can
correlate the target treatment site with an identifiable anatomical
structure (e.g., a spinal feature) and/or a radiopaque ruler
positioned under or on the patient before delivering the radiation
unit 120 to the target site. Further, in some embodiments, image
guidance components (e.g., IVUS or OCT) may be integrated with the
treatment device 100 and/or running parallel with the treatment
device 100 to provide image guidance during positioning of the
radiation unit 120. This can be carried out by coupling IVUS, OCT
or other image-guidance components to a distal portion of the shaft
100 to provide three-dimensional images of the vasculature
proximate to the target site to facilitate positioning or deploying
the radiation unit 120 within the target blood vessel. In the
specific example shown in FIG. 1, the radiation unit 120 is
positioned in the renal artery (RA) at a suitable location between
the renal ostium (RO) and the kidney (K).
[0027] After the radiation unit 120 has been positioned at a
treatment location, the radiation unit 120 can be transformed or
otherwise manipulated from a low-profile delivery state suitable
for passing through the vasculature (e.g., the femoral artery (FA),
the iliac artery (IA), and aorta (A)) to a deployed state in a
target vessel (e.g., the renal artery (RA)). In the deployed state,
for example, the radiation unit 120 can securely contact the wall
of the blood vessel or other body lumen to stabilize the radiation
unit 120 for delivering energy to the target nerves. In some
embodiments, the radiation unit 120 may be delivered to a treatment
site using a guide sheath (not shown) with or without using a guide
wire. When the radiation unit 120 is at the target site, the guide
sheath may be at least partially withdrawn or retracted so that the
radiation unit 120 can transform to the deployed state. For
example, the radiation unit 120 can have a balloon, basket, spiral
member (e.g., helical), or other suitable positioning member that
can be inflated, self-expanded, or manipulated by a wire to move
from the delivery state to the deployed state. In some other
embodiments, the shaft 110 may itself be steerable such that the
radiation unit 120 can be delivered to the treatment site without
the aid of a guide wire and/or guide sheath.
[0028] FIG. 2 is a schematic cross-sectional view of a distal
portion of the treatment device 100 at a target site in a body
lumen 200, such as a blood vessel, airway, or other naturally
occurring passageway. The radiation unit 120 can include a
positioning member 112 at the distal end of a shaft 110 and an
emitter 122. The positioning member 112 can be expanded to contact
the inner wall of the body lumen 200 such that the emitter 122 is
positioned at a desired location relative to the target site. The
positioning member 112, for example, can be a balloon, basket,
spiral member, or other structure. In one embodiment, the emitter
122 is an optical element coupled to a fiber optic line 124 that
extends to an external radiation source. In other embodiments, the
emitter 122 itself can be a radiation source coupled to an
electrical lead that generates the radiation from within the body
lumen 200. For example, the emitter 122 can be a light emitting
diode (LED) or an array of LEDs. When the emitter 122 is centered
in the body lumen as shown in FIG. 2, the positioning member 112 is
generally expanded using an inflation medium that does not overly
attenuate the energy of the radiation such that the positioning
member contacts the inner wall of the body lumen so that blood does
not absorb the energy of the radiation.
[0029] FIG. 2 further illustrates an embodiment of the operation of
the treatment device 100. After the positioning member 112 has been
transformed into the deployed state in which it contacts at least a
portion of the inner wall of the body lumen 200, radiation 130 is
delivered from the emitter 122. The radiation 130 passes through
the positioning member 112, tissue 202 and 204 of the inner wall of
the body lumen 200, and nerves 206 in the tissue around the body
lumen 200. When the body lumen 200 is a blood vessel, such as the
renal artery, tissue 202 can be the intimal tissue, tissue 204 can
be the medial tissue, and the nerves 206 can be the renal nerves.
The radiation 130 is applied to the nerves 206 after a sufficient
quantity of the photosensitizer 208 has accumulated at the nerves
206 and either before an undesirable amount of the photosensitizer
has accumulated in and/or in the tissues 202 and 204 or after a
sufficient quantity of photosensitizer 208 has dissipated from the
tissues 202 and 204. In several embodiments, the photosensitizer
208 can accumulate in and/or on the nerves 206 by preferentially
binding to the nerves 206 as shown schematically in FIG. 2. The
radiation 130 causes to the photosensitizer 208 to react such that
the photosensitizer 208 damages or otherwise disrupts at least the
nerves 206. For example, the photosensitizer 208 can become toxic
to the nerves 206 and possibly the other tissues proximate the
nerves 206. Since the concentration of the photosensitizer 208 is
greater at the nerves 206 than the tissues 202 and 204, greater
damage is caused to the nerves 206. Thus, several embodiments for
therapeutically modulating perivascular nerves in a human in
accordance with the present technology selectively disrupt the
perivascular nerves such that neural communication is at least
partially inhibited along the targeted perivascular nerves without
disrupting the function of the other tissues of the wall of the
blood vessel.
Selected Embodiments of Photosensitizers and Dosages
[0030] The photosensitizer 208 can be any suitable compound that
preferentially accumulates at neural tissue compared to other
tissues proximate the nerves. For example, the photosensitizer 208
can accumulate in and/or on the neural tissue over a period of time
to a greater extent than other tissue proximate the neural tissue.
In one embodiment, the photosensitizer can be oxytetracycline, a
suitable tetracycline analog, or other suitable photosensitive
compounds that preferentially bind to neural tissue.
Oxytetracycline is expected to preferentially bind to calcium in
the nerves such that more oxytetracycline remains at the nerves
than in the non-neural tissue proximate to the nerves after a
sufficient period of time has elapsed after administering the
oxytetracycline.
[0031] When the photosensitizer 208 is oxytetracycline, the
radiation delivered from the emitter 122 has a wavelength of 350
nm-365 nm, and often more specifically 351 nm-355 nm. In one
particular embodiment, the oxytetracycline is administered at a
dosage of 0.5-1 mg/kg, and in other embodiments the oxytetracycline
can be administered at a dosage of 1-49 mg/kg, 50-300 mg/kg, or
300-600 mg/kg. The radiation can have a dosage of 0.5-5 J/cm.sup.2,
5-25 J/cm.sup.2, 25-100 J/cm.sup.2, or 100-500 J/cm.sup.2 depending
on a number of parameters such as the thickness and type of tissue
between the radiation emitter and the target neural tissue, and the
radiation can be continuous or pulsed irradiation exposure. In the
case of pulsed radiation, the pulse rate can be approximately 10-50
ps, 15-40 ps, 20-30 ps, or 20-25 ps (e.g., 24 ps). The
oxytetracycline can be administered approximately 30-180 minutes,
or 3-24 hours, before being irradiated with radiation at a
wavelength of approximately 351 nm-365 nm.
[0032] In another example, the photosensitizers can be
furocoumarins (psoralens) or porphyrins administered at a dosage of
0.5-1 mg/kg, 1-49 mg/kg, 50-300 mg/kg, or 300-600 mg/kg.
Approximately 30-180 minutes, or 3-24 hours, after administering
the furocoumarins (psoralens) or porphyrins, a radiation dosage of
0.5-5 J/cm.sup.2, 5-25 J/cm.sup.2, 25-100 J/cm.sup.2, or 100-500
J/cm.sup.2 is delivered to the target site.
[0033] In another example, the photosensitizers can be
benzoporphyrin or a derivative of benzoporphyrin (such as
lemuteporfin) administered at a dosage of 0.5-1 mg/kg, 1-49 mg/kg,
50-300 mg/kg, or 300-600 mg/kg. Approximately 30-180 minutes, or
3-24 hours, after administering the lemuteporfin, a radiation
dosage of 0.5-5 J/cm.sup.2, 5-25 J/cm.sup.2, 25-100 J/cm.sup.2, or
100-500 J/cm.sup.2 is delivered to the target site.
[0034] In another example, the photosensitizers can be
phthalocyanines administered at a dosage of 0.5-1 mg/kg, 1-49
mg/kg, 50-300 mg/kg, or 300-600 mg/kg. Approximately 30-180
minutes, or 3-24 hours, after administering the lemuteporfin, a
radiation dosage of 0.5-5 J/cm.sup.2, 5-25 J/cm.sup.2, 25-100
J/cm.sup.2 or 100-500 J/cm.sup.2 is delivered to the target
site.
Additional Embodiments of Photodynamic Neuromodulation Devices
[0035] FIG. 3A is a schematic cross-sectional view of a treatment
device 300 for therapeutic neuromodulation in accordance with the
present technology, and FIG. 3B is a cross-sectional view of the
treatment device 300 taken along line B-B of FIG. 3A. Referring to
FIG. 3A, the treatment device 300 can include an elongated shaft
310 having a plurality of openings 311a-b and a radiation unit 320
attached to a distal portion of the shaft 310. The radiation unit
320 can include a positioning member 312 attached to the shaft 310
and an emitter 322 configured to deliver radiation through the
openings 311a-b such that the radiation projects radially outward
with respect to the shaft 310. The radiation passes through a
chamber 313 defined by the positioning element 312 to irradiate the
target tissue as explained above. The emitter 322 can be an optical
element coupled to a fiber optic cable 324 that directs the light
in the desired radial distribution relative to the shaft 310. The
radiation source in such embodiments can be positioned at an
extracorporeal location and configured to direct light through the
fiber optic cable 324 to the emitter 322. In other embodiments, the
emitter 322 can be an internal radiation source, such as an LED or
other small radiation emitter. The emitter 322, for example, can be
an array of one or more LEDs that emit radiation in a desired
bandwidth.
[0036] Referring to FIG. 3B, the positioning element 312 can be an
inflatable balloon having a first portion 314 configured to contact
an inner wall of a blood vessel or another body lumen in a deployed
state. For example, other body lumens can be the esophagus,
trachea, lung airways, and/or the gastro-intestinal system. The
first section 314 is configured to securely position the emitter
322 at a desired location with respect to the target tissue in the
deployed state. The positioning element 312 can further include a
second portion 316 defining a channel or other external passageway
configured to allow blood, air, or another body fluid to pass
through the channel when the positioning element 312 is in the
deployed state (e.g., inflated or expanded to securely position the
emitter 322 at a desired location with respect to the target
tissue). The radiation emitter 320 is expected to be particularly
useful for applications in the renal artery because it only
partially occludes the blood vessel to allow blood flow during the
procedure. This will allow exposure times longer than the 2-5
minutes that the renal arteries can be occluded, if necessary.
[0037] FIG. 4 is a schematic cross-sectional view of another
embodiment of a treatment device 400 in accordance with the present
technology for therapeutically modulating neural function. The
treatment device 400 can include an elongated shaft and a radiation
unit 420 having a positioning member 412 defined by an expandable
basket having a plurality of supports 414. The proximal ends of the
supports 414 are attached to a proximal hub 416a, and the distal
end of the supports 414 are attached to a distal hub 416b. At least
one of the proximal and distal hubs 416a and 416b is moveable along
the longitudinal dimension of the shaft 410 to transform the
positioning member 412 from a low-profile delivery state to an
expanded deployed state in which the supports 414 contact in inner
wall of a body lumen (BL) at a target site. The radiation unit 420
further includes a plurality of radiation emitters 422 attached to
the supports 414. The radiation emitters 422 can be optical
elements coupled to fiber optic cables for delivering radiation
from a radiation source at an extracorporeal location to the target
tissue at the body lumen (BL). In other embodiments, the radiation
emitters 422 can be internal radiation sources, such as LEDs, that
are electrically coupled to a power source at an extracorporeal
location via electrical leads within the shaft 410. In the
embodiment shown in FIG. 4, the radiation emitters 422 are
angularly spaced apart from each other around a longitudinal
dimension A-A of the shaft 410 at a common area along the length of
the longitudinal dimension A-A. This arrangement of radiation
emitters 422 provides a circumferential exposure in a common plane
perpendicular to the longitudinal dimension A-A of the shaft
410.
[0038] In operation, a photosensitizer is administered to the
patient as described above and the treatment device 400 is
positioned at the target site with the supports 414 in the
low-profile delivery state. The supports 414 are expanded to the
deployed state such that the radiation emitters 422 contact the
inner wall of the body lumen (BL) or are positioned apart from the
inner wall of the body lumen depending on the type of fluids within
the body lumen. For example, in the case of blood vessels or other
body lumens with fluids that attenuate the radiation, the supports
are generally expanded such that the emitters 422 contact the
vessel wall to directly irradiate the inner wall of the vessel so
that blood does not block the radiation. Radiation is then
delivered to the target neural tissue from the radiation emitters
422 to react the photosensitizer as described above.
[0039] FIG. 5 is a cross-sectional view of another embodiment of a
treatment device 500 in accordance with the present technology for
delivering radiation to target tissue. The treatment device 500 can
be similar to the treatment device 400 shown in FIG. 4, and like
reference numbers refer to similar or identical components in these
figures. Referring to FIG. 5, the treatment device 500 has one or
more proximal radiation emitters 422a coupled to first supports
414a and one or more distal radiation emitters 422b coupled to
second supports 414b. The proximal and distal radiation emitters
422a and 422b are spaced longitudinally apart from each other along
the length of the longitudinal dimension A-A of the shaft 410, and
the proximal and distal radiation emitters 422a and 422b are also
angularly offset from each other relative to the longitudinal
dimension A-A. Although eight supports 414 and eight radiation
emitters 422 are shown in FIG. 5, any suitable number supports and
emitters may be used. For example, the treatment device 500 may
have two first supports 414a, two first proximal radiation emitters
422a (one on each first support 414a), two second supports 414b,
and two distal radiation emitters 422b (one on each second support
414b). Such a configuration of proximal and distal radiation
emitters provides angularly offset exposure zones such that the
radiation does not completely expose the full circumference of the
lumen in a plane perpendicular to the longitudinal dimension A-A of
the shaft.
[0040] FIG. 6 is a cross-sectional view of another embodiment of a
treatment device 600 in accordance with the present technology. The
treatment device 600 is similar to the treatment devices 400 and
500, and like reference numbers refer to similar or identical
components in FIGS. 4-6. The treatment device 600 has first-fourth
supports 414a-d, respectively, and first-fourth radiation emitters
422a-d, respectively. The radiation emitters 422a-d are spaced
apart from each other at different longitudinal and angular
locations with respect to the longitudinal dimension A-A of the
shaft 410 such that the radiation is delivered to different
longitudinal and angular locations along the inner wall of the body
lumen (BL). This arrangement of emitters provides another pattern
of non-circumferential exposure zones.
[0041] The positioning elements 412 of the treatment devices 400,
500 and 600 shown in FIGS. 4-6 can be self-expanding baskets or
pull-wire actuated baskets. For example, self-expanding supports
414 can comprise a shape-memory metal, or they can be springs that
expand outwardly after being released from a sheath. In pull-wire
embodiments, the distal hub 416b can be coupled to a pull-wire to
expand the supports 414 outwardly when the pull-wire is retracted
proximally.
[0042] FIG. 7 is a cross-sectional view of an embodiment of a
treatment device 700 for therapeutically modulating neural function
in accordance with the technology. The treatment device 700 can
include an elongated shaft 710 and a radiation unit 720 having a
positioning element 712 at a distal portion of the shaft 710 and a
plurality of radiation emitters 722 coupled to the positioning
element 712. In the illustrated embodiment, the positioning element
712 is a balloon and the radiation emitters 722 are arranged such
that they are spaced apart from each other longitudinally and
angularly with respect to the longitudinal dimension A-A of the
shaft 710. The device 700 can include a suitable number of
radiation emitters 722 depending on the size of the body lumen
(BL). For example, 2, 4, 6, 8, 10 or 12 radiation emitters 722 can
be spaced apart from each other angularly and/or longitudinally
with respect to the longitudinal dimension A-A of the shaft 710 to
provide the desired pattern of radiation along the inner wall of
the body lumen (BL).
[0043] FIG. 8 is a partial cross-sectional side view of a treatment
device 800 for therapeutically modulating neural function in
accordance with another embodiment of the present technology. The
treatment device 800 includes an elongated shaft 810 and a
radiation unit 820 having a positioning member 812 and a plurality
of radiation emitters 822 coupled to the positioning member 812. In
this embodiment, the positioning member 812 is a self-expanding or
pull-wire actuated member that has a substantially linear
low-profile delivery state configured to be contained in a sheath
and a spiral (e.g., helical) deployed state configured to position
in the emitters 812 against the inner wall of the body lumen (BL).
The positioning element 812 can be a helix with a constant pitch
and diameter, or the helix can have a pitch and/or diameter that
varies at different portions along the positioning member 812.
[0044] FIG. 9 is an isometric view having a cut-away portion
showing a distal portion of a treatment device 900 for therapeutic
neuromodulation in accordance with an embodiment of the present
technology. The treatment device 900 can include a shaft 910 and a
radiation unit 920 attached to a distal portion of the shaft 910.
The radiation unit 920 can include a positioning member 912 defined
by a balloon and a radiation emitter 922 carried by the shaft 910
within the positioning member 912. The radiation emitter 922 can
include a fiber optic cable 924 configured to transmit
electromagnetic radiation from a source to the radiation unit 920
and a reflector 925 configured to direct the electromagnetic
radiation from the fiber optic cable 924 to target tissue outside
of the radiation unit 920. In one embodiment, the reflector 925 has
a base 926 mounted to or otherwise carried by the shaft 910, a slot
927 at a proximal end of the base 926 to retain a distal end of the
fiber optic cable 924, and an inclined reflective surface 928
configured to direct light transmitted through the fiber optic
cable 924 at non-parallel angles (e.g., transverse) to the
longitudinal axis of the shaft 910. In one embodiment, the inclined
reflective surface 928 is in a plane at an angle of 45.degree.
relative to the shaft to direct light through the positioning
member 912 perpendicularly to the shaft 910. In other embodiments,
the inclined surface 928 can be at other angles to direct the light
at transverse angles with respect to the shaft 910. The inclined
surface 928 can be spaced apart from the distal terminus of the
fiber optic cable 924 by a channel 929.
[0045] The reflector 925 can be made of glass, silicon, metals, or
other materials covered with reflective materials. In other
embodiments, the reflector 925 can be a prism with an inclined
surface or other structure that deflects the light in a desired
direction. In still other embodiments, the radiation unit 920 may
not include the reflector, but instead the fiber optic cable 924
can be bent or have a tip that diverts the radiation at a desired
angle with respect to the shaft 910.
[0046] The balloon-type positioning member 912 can be filled with a
saline solution or other solution through which the light can pass.
In one embodiment, the shaft 910 and positioning member 912 are
configured to provide fluid flow through the positioning member 912
to cool the tissue being irradiated. Although cooling is not
necessary in many embodiments, some photonic methods may cause the
tissue of the inner wall of the body lumen to heat to temperatures
that can be uncomfortable or otherwise undesirable. The fluid flow
through the positioning member 912 is accordingly useful in such
situations to maintain the temperature of the inner wall of the
body lumen. Additionally, the radiation unit 920 can include a
temperature sensor on the positioning member 912 to monitor the
temperature of the tissue. The temperature sensor, for example, can
be mounted to the surface of a balloon-type positioning member 912
to accurately sense the temperature at the inner wall of the body
lumen.
[0047] FIG. 10 is an isometric view further illustrating an
embodiment of operating the radiation unit 920. The light (L) is
projected from the terminus of the fiber optic cable 924 and
reflected from the inclined surface 928 to form a light cone (LC)
that projects out of the positioning element 912 (FIG. 9). The
light cone (LC) can be rotated such that it continuously scans the
full circumference of the inner wall of the body lumen, or the
light cone (LC) can irradiate one or more discrete areas of the
inner wall. For example, the shaft 910 and the radiation unit 920
can be rotated (R) around a guide wire (GW) such that the light
cone (LC) continuously irradiates a full 360.degree. circumference
of the body lumen or intermittently irradiates only discrete areas
around the circumference of the body lumen. In this embodiment, the
positioning member 912 can be freely rotated within the body lumen
because the positioning member 912 is inflated so that it
substantially occludes the body lumen without contacting the inner
wall of the body lumen. In another embodiment, the reflector 925
and the fiber optic cable 924 can be mounted onto a separate shaft
that can rotate with respect to the shaft 910. This allows the
positioning member 912 to be inflated such that the positioning
member 912 contacts the inner wall and remains stationary with
respect to the body lumen while the reflector 925 and the fiber
optic cable 924 rotate and scan the light cone (LC) around the body
lumen. The radiation unit 920 can also be translated along the
longitudinal direction of the body lumen and rotated to provide a
continuous helical lesion or a plurality of separate lesions having
a helical/spiral pattern or other desired pattern.
[0048] In another embodiment of the treatment device shown in FIGS.
9 and 10, the radiation unit 920 can include a plurality of fiber
optic cables and a corresponding plurality of reflectors 925. For
example, two reflectors 925 could be mounted on opposite sides of
the shaft 910 and two fiber optic cables 924 could extend along the
length of the shaft 910 such that two separate light cones project
from opposite sides of the positioning member 912. Similarly, any
number of reflectors can be arranged in an array along the length
of the shaft 910 and/or around the circumference of the shaft 910
to form a continuous circumferential or spiral lesion, or several
lesions in a circumferential, spiral, offset, or other pattern.
[0049] The radiation emitters 422, 722, 822 and 922 shown in FIGS.
4-10 can be independently operable to provide a desired radiation
pattern. As such, only certain emitters may be active for a
particular procedure or for a specific patient. The emitters can be
fired simultaneously, or in other embodiments the emitters can be
fired sequentially or in different groups or other patterns.
Additionally, the radiation units 120, 320, 420, 720, 820 and 920
can be activated at several different locations along the length of
a vessel and at different rotational orientations within a vessel.
For example, referring to FIG. 1, the radiation unit 120 can be
activated at the location shown for a suitable period to
sufficiently irradiate the photosensitizer at that location. The
radiation unit 120 can then be transformed to a low-profile state,
moved distally or proximally along the renal artery (RA) to a
different location, transformed to a deployed state, and then
re-activated to irradiate another area of the renal artery (RA).
The procedure can also be performed in both the left and right
renal arteries for a bi-lateral therapy.
[0050] Additionally, other embodiments of treatment devices can
have a fiber optic cable or an in vivo emitter at a distal tip of
the shaft that can be placed against the inner wall of a body lumen
to irradiate discrete areas. For example, the device in
International Publication No. WO 2008/003058, filed Jun. 28, 2007,
and incorporated by reference herein, can be modified to have a
fiber optic cable and/or an LED at the distal tip in addition to or
in lieu of an electrode.
[0051] FIG. 11 is a schematic view of a system having a controller
1100 that includes a control algorithm 1110 for operating any of
the treatment devices 100, 300, 400, 500, 600, 700, 800 and 900
described above with reference to FIGS. 1-10. The controller 1000
can optionally include a radiation source 1020 that generates the
radiation for transmission via fiber optic lines or other light
guides through the shaft of the treatment device to the radiation
emitters 122, 322, 422, 722, 822 and 922 at the distal end of the
shaft. In other embodiments, the controller includes a power source
electrically coupled to LED type or other in vivo radiation
emitters 122, 322, 422, 722, 822 and 922 at the distal end of the
shaft. The algorithm 1110 can include instructions contained on a
computer operable medium that operates the radiation emitters to
provide the desired radiation pattern and extent of irradiation. In
one embodiment, the algorithm 1110 causes the controller 1100 to
deliver radiation via the radiation emitter(s) 122, 322, 422, 722,
822 and 922 at a wavelength of 350 nm-365 nm, and in some
embodiments within the range of 351 nm-355 nm. The controller 1000
can further cause 0.5-5 J/cm.sup.2, 5-25 J/cm.sup.2, 25-100
J/cm.sup.2, or 100-500 J/cm.sup.2 of radiation to be delivered. Any
of the foregoing ranges of radiation dosage can be delivered from a
single emitter or from each emitter of a plurality of emitters.
Selected Applications, Test Results and Examples
[0052] Several embodiments of the present technology can be used
intravascularly in the renal arteries, renal ostium, renal veins,
renal pelvis, renal calyx (e.g., through the ureter), and/or the
renal branch arteries near the renal parenchyma to affect the renal
plexus/renal nerve including afferent renal nerves and/or efferent
renal nerves. Applications that target the renal plexus/renal nerve
through the renal artery, renal ostium and/or renal vein are often
directed to treating hypertension, left ventricular hypertrophy,
ventricular arrhythmias, sudden cardiac death, insulin resistance,
diabetes, metabolic syndrome, hyperaldosteronism, erectile
dysfunction, Polycystic Ovary Syndrome (PCOS), infertility
(female), Polycystic Kidney Disease (PKD), renal failure, and pain
associated with the kidneys. Applications that target efferent
renal nerves at the renal pelvis or renal calxy (e.g., through the
ureter) can be directed toward decreasing central sympathetic drive
to treat hypertension, other cardiac conditions, diabetes, etc.
Treatments that target efferent and/or afferent renal nerves at the
renal artery and/or the renal branch arteries can be used for
treating kidney disease (PKD, renal failure, etc.) and reducing
central sympathetic drive (e.g., for treatment of hypertension in
patients diagnosed having cystinuria or having an increased risk of
developing kidney stones).
[0053] Several other non-renal nerve targets, treatment locations,
and diseases/conditions/etiologies are listed below in TABLE 1. In
each of these additional non-renal applications, the
photosensitizer is administered to the patient and the radiation
unit of the treatment device is intravascularly positioned at the
treatment location to target the nerves for treating the particular
disease, condition, and/or etiology as set forth in TABLE 1.
TABLE-US-00001 TABLE 1 Intravascular Nerve Target treatment
location Disease/Condition/Etiology Ovarian Ovarian Artery/Vein
PCOS, infertility plexus/Ovarian Nerve Spermatic Testicular
Artery/Vein Testicular pain (orchialgia) Plexus Genital branch of
External iliac Testicular pain (orchialgia), vasectomy
genitofemoral artery/vein, testicular complications, vulvodynia,
pain associated with nerve (Lumbar vessels, scrotum, Plexus)
Ilioinguinal nerve Deep circumflex iliac Pain associated with
injury, scrotal skin, skin over (Lumbar Plexus) artery (or vein)
which the root of the penis, groin is a branch of the external
iliac artery Sacral Plexus Internal iliac artery, Genital (male and
female) pain (orchialgia, internal iliac vein vulvodynia,
clitorodynia, injury) Pudendal nerve Internal pudendal Genital
(male and female) pain (orchialgia, (sacral plexus) vessels
(artery) vulvodynia, clitorodynia), erectile dysfunction Perineal
nerve Internal pudendal Genital (male and female) pain (orchialgia,
(from pudendal artery vulvodynia, clitorodynia, scrotum) nerve)
Vaginal plexus Branches of the Pain or spasm (vaginismus)
associated with vagina internal iliac artery and clitoris (e.g.,
vaginal arteries, vaginal venous plexus) Uterine Plexus Uterine
artery Uterine pain, vaginal pain, vaginismus Lumbosacral Internal
iliac artery, Pain in pelvic region plexus (anterior internal iliac
vein, the divisions of the ureter, superior lumbar nerves, gluteal
artery and sacral nerves, vein and coccygeal nerve) Celiac Plexus
Celiac Artery Pain in abdominal viscera (pancreas (pancreatitis,
pancreatic cancer), Hepatobiliary diseases (liver and biliary tract
and gallbladder), spleen (inflammation, leukemia, lymphoma, etc),
stomach (cancer), small intestine and large bowel (cancer), kidney)
Superior Superior Mesenteric Pain associated with pancreas
(pancreatitis, Mesenteric Artery/Vein pancreatic cancer) and small
intestine and colon Plexus (cancer); treatment of gastrointestinal
disorders (inflammatory bowel disease, e.g., Crohn's disease and
ulcerative colitis) Hepatic plexus Hepatic artery Pain associated
with Hepatobiliary diseases (liver and biliary tract and
gallbladder) Splenic plexus Splenic artery/vein, Pain associated
with spleen (inflammation, leukemia, splenic branch lymphoma, etc),
treat inflammation (e.g., overactive arteries immune response),
inflammation associated with autoimmune diseases (Multiple
sclerosis, lupus, psoriasis) Gastric plexus Gastric artery,
Gastrointestinal disorders (inflammatory bowel superior mesenteric
disease, e.g., Crohn's disease and ulcerative colitis, artery/vein,
inferior collagenous colitis, lymphocytic colitis, ischaemic
mesenteric colitis, diversion colitis, and Behcet's disease),
artery/vein obesity, overeating Pancreatic Pancreatic artery Pain
associated with pancreas (pancreatitis, plexus pancreatic
cancer)
[0054] Several embodiments of the present technology are also
applicable to extravascular locations. For example, neural
structures such as ganglia, peripheral nerves, spinal nerves,
cranial nerves, and/or cortical or deep brain neural structures can
be modulated in accordance with the present technology. In these
embodiments, a neural photosensitizer is administered to the
patient and a percutaneous treatment device with a radiation unit
is inserted into the patient and positioned proximate to the target
neural structures. The treatment device, for example, can be a
probe or surgical instrument that can penetrate tissue, and the
radiation unit can have a fiber optic emitter and/or internal
radiation source at a distal end of the probe. The
photosensitizers, radiation, and dosages can be any of the
foregoing dosages used for intravascular applications.
[0055] The selective disruption of neural cells using
oxytetracycline was evaluated to determine whether irradiated
oxytetracycline produced a lower cell count compared to control
cells. PC12 cells were seeded into collagen coated 96 well plates,
and a nerve growth factor (NGF) was added seven days before PC12 to
induce cell differentiation. To determine an amount of UVA
radiation that would have a nominal effect on cell death, the cells
were exposed to titrating amounts of radiation, and then
post-exposure cells were incubated for 24 hours before being washed
twice, allowed to incubate for one hour, stained with Pico Green,
and then counted using a Wallace plate reader. FIG. 12 is a graph
showing that at a treatment time of 30-60 seconds the UVA alone
started to reduce the cell count. An exposure time of 1 minute was
selected for the test as being representative of an exposure where
UVA would not significantly affect cell count. Another test was
performed to assess the cell count of smooth muscle cells (SMC) and
PC12 cells treated with oxytetracycline without irradiation. In
this procedure, SMC and PC12 cells were seeded into collagen
dishes, NGF was added seven days before PC12 to induce cell
differentiation, both the SMC and PC12 cells were dosed with
titrating amounts of tetracycline (e.g., 0 .mu.g/ml, 20 .mu.g/ml,
200 .mu.g/ml, and 2 mg/ml), the oxytetracycline dosed cells were
incubated for 24 hours, and then the cells were stained with
Calcein AM-EtBr 1 .mu.M for 30 minutes. FIG. 13 is a series of
views showing the cell loss (dark areas) due to the
oxytetracycline. Based on FIG. 13, a dosage of 20 .mu.g/ml was
selected as an amount that generally produced the same cell count
in SMC and PC12 cells over a 24 hour incubation period.
[0056] The final phase of the test included seeding PC12 cells into
collagen coated 96 plates. An NGF was added seven days before PC12
cells to induce cell differentiation. The control cells and the
PC12 cells were then dosed with 20 .mu.g/ml of oxytetracycline for
24 hours. The test cells were exposed to UVA radiation at a
wavelength of approximately 365 nm using an LEDMOD.RTM. Series
Laser manufactured by Omicron-Laser, Germany, and an X-Cite.RTM.
optical power measurement system, Lumen Dynamics Group, Inc.,
washed twice, stained with Pico Green, and then counted using a
Wallace plate reader. FIG. 14 is a graph showing that the cells
irradiated by the oxytetracycline were approximately 20% less than
the cells of the carrier control group that were not irradiated.
This test shows that neuronal cells exposed to UVA radiation and a
dosage of oxytetracycline have a lower survival rate than the
control cells.
EXAMPLES
Example 1
[0057] A method for therapeutic neural denervation in a human,
comprising: [0058] administering a photosensitizer to a human,
wherein the photosensitizer preferentially accumulates at nerves
proximate a blood vessel compared to non-neural tissue of the blood
vessel; and [0059] irradiating the photosensitizer using a
radiation emitter positioned within the human, wherein the
radiation has a wavelength that causes the photosensitizer to react
and alter at least a portion of the nerves thereby providing a
therapeutic reduction in sympathetic neural activity.
Example 2
[0060] A therapeutic neural modulation method in a human for
therapeutically reducing sympathetic neural activity, comprising:
[0061] providing a photosensitizer to perivascular neural tissue
associated with sympathetic neural activity, wherein the
photosensitizer selectively binds to perivascular neural tissue
compared to non-neural vascular tissue; [0062] positioning a
radiation emitter of treatment device in a blood vessel of the
human at a target site for the perivascular neural tissue; and
[0063] emitting radiation from the radiation delivery device such
that the perivascular neural tissue is irradiated by the radiation,
wherein the radiation causes the photosensitizer to react and
thereby disrupt the perivascular neural tissue such that neural
communication along the perivascular neural tissue is at least
partially inhibited.
Example 3
[0064] A method for operating a photodynamic system, comprising:
[0065] providing a photosensitizer that preferentially binds to
calcium; [0066] generating radiation at a wavelength; and [0067]
delivering the radiation to the photosensitizer.
Example 4
[0068] The method of any of examples 1-3, wherein the radiation has
a wavelength of 350 nm-365 nm.
Example 5
[0069] The method of any of examples 1-3, wherein the radiation has
a wavelength of 351 nm-355 nm.
Example 6
[0070] The method of any of examples 1-5, wherein the
photosensitizer is administered or provided at a dosage of 0.5-1
mg/kg.
Example 7
[0071] The method of any of examples 1-5, wherein the
photosensitizer is administered or provided at a dosage of 1-49
mg/kg.
Example 8
[0072] The method of any of examples 1-5, wherein the
photosensitizer is administered or provided at a dosage of 50-300
mg/kg.
Example 9
[0073] The method of any of examples 1-5, wherein the
photosensitizer is administered or provided at a dosage of 300-600
mg/kg.
Example 10
[0074] The method of any of examples 1-9, wherein the radiation has
a dosage of 0.5-1 J/cm.sup.2.
Example 11
[0075] The method of any of examples 1-9, wherein the radiation has
a dosage of 5-25 J/cm.sup.2.
Example 12
[0076] The method of any of examples 1-9, wherein the radiation has
a dosage of 25-100 J/cm.sup.2.
Example 13
[0077] The method of any of examples 1-9, wherein the radiation has
a dosage of 100-500 J/cm.sup.2.
Example 14
[0078] The method of any of examples 1-13, wherein the radiation is
pulsed at a pulse rate of 2 ps-50 ps.
Example 15
[0079] The method of any of examples 1-14, wherein the
photosensitizer is administered or provided approximately 30-180
minutes before irradiating the photosensitizer.
Example 16
[0080] The method of any of examples 1-14, wherein the
photosensitizer is administered or provided approximately 3-24
hours before irradiating the photosensitizer.
Example 17
[0081] The method of any of examples 1-16, wherein the
photosensitizer becomes toxic to the nerves proximate the blood
vessel upon reacting with the radiation without impairing function
of the non-neural tissue of the blood vessel.
Example 18
[0082] The method of any of examples 1-17, wherein the
photosensitizer preferentially binds to calcium in the nerves
proximate the blood vessel.
Example 19
[0083] The method of any of examples 1-18, wherein administering or
providing the photosensitizer comprises injecting the
photosensitizer into tissue for systemic distribution of the
photosensitizer.
Example 20
[0084] The method of any of examples 1-18, wherein administering or
providing the photosensitizer comprises orally ingesting the
photosensitizer for systemic distribution of the
photosensitizer.
Example 21
[0085] The method of any of examples 1-18, wherein administering or
providing the photosensitizer comprises injecting the
photosensitizer proximate perivascular nerves that extend along the
blood vessel.
Example 22
[0086] The method of any of examples 1-21, wherein irradiating the
photosensitizer comprises inserting a catheter into the renal
artery and directing the radiation through the renal artery wall to
renal nerves.
Example 23
[0087] The method of any of examples 1-22, wherein irradiating the
blood vessel includes emitting the radiation in a spiral pattern
about an inner wall of the blood vessel.
Example 24
[0088] The method of any of examples 1-22, wherein irradiating the
blood vessel includes emitting the radiation at a plurality of
locations spaced apart from each other at offset circumferential
positions along a length of the blood vessel.
Example 25
[0089] The method of any of examples 1-22, wherein irradiating the
blood vessel includes emitting a circumferential pattern of
radiation around a common plane perpendicular to the blood
vessel.
Example 26
[0090] The method of any of examples 1-25, further comprising
positioning the radiation emitter in a blood vessel as set forth in
TABLE 1 for modulating the corresponding target nerve and thereby
treating the corresponding disease/condition/etiology.
Example 27
[0091] The method of any of examples of 1-26, wherein the
photosensitizer comprises oxytetracycline.
Example 28
[0092] The method of any of examples 1-26, wherein the
photosensitizer comprises furocoumarins.
Example 29
[0093] The method of any of examples 1-26, wherein the
photosensitizer comprises prophyrins.
Example 30
[0094] The method of any of examples 1-26, wherein the
photosensitizer comprises benzoporphyrin or a derivative
thereof.
Example 31
[0095] The method of any of examples 1-26, wherein the
photosensitizer comprises phthaloxyanines.
Example 32
[0096] A system for performing photodynamic therapy, comprising:
[0097] a treatment device having an elongated shaft and a radiation
unit at a distal portion of the elongated shaft, wherein the
radiation unit has a positioning member and at least one radiation
emitter, and wherein the positioning member is configured to have a
low-profile delivery state for intravascular passage to a target
site and a deployed state in which the positioning member is
configured to contact a wall of a body lumen such that the
radiation emitter is stabilized at a desired location relative to
target tissue; and [0098] a controller configured to be coupled to
the treatment device, wherein the controller is adapted to cause
radiation at a wavelength of 351 nm-365 nm to be delivered from the
radiation unit to deliver 0.5-5 J/cm.sup.2, 5-25 J/cm.sup.2, 25-100
J/cm.sup.2, or 100-500 J/cm.sup.2 of radiation to a target.
Example 33
[0099] The system of example 32, wherein the controller has a
radiation source and the radiation emitter of the radiation unit
comprises an optic element configured to distributed the radiation
to the target tissue, and wherein the system further comprises a
light guide coupled to the controller and the optic element to
transmit the radiation from the controller to the optic
element.
Example 34
[0100] The system of example 32, wherein the controller has a power
source and the radiation emitter of the radiation unit comprises a
radiation generator coupled to the positioning member, and wherein
the system further comprises an electrical lead electrically
coupled to the power source and the radiation generator.
Example 35
[0101] The system of example 34, wherein the radiation generator
comprises a light emitting diode.
Example 36
[0102] The system of example 34, wherein the radiation generator
comprise an array of light emitting diodes.
Example 37
[0103] A device for therapeutically modulating sympathetic neural
system activity, comprising: [0104] an elongated shaft configured
to pass through vascular passages of a human; [0105] a balloon at a
distal portion of the elongated shaft, the balloon having a wall
configured to contact an inner wall of a blood vessel and an
exterior channel through which blood can flow when inflated to a
deployed state; and [0106] a radiation element at the balloon
configured to deliver radiation to perivascular nerves along the
blood vessel.
CONCLUSION
[0107] 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.
[0108] Certain aspects of the present technology may take the form
of computer-executable instructions, including routines executed by
a controller or other data processor. In some embodiments, a
controller or other data processor is specifically programmed,
configured, and/or constructed to perform one or more of these
computer-executable instructions. Furthermore, some aspects of the
present technology may take the form of data (e.g., non-transitory
data) stored or distributed on computer-readable media, including
magnetic or optically readable and/or removable computer discs as
well as media distributed electronically over networks.
Accordingly, data structures and transmissions of data particular
to aspects of the present technology are encompassed within the
scope of the present technology. The present technology also
encompasses methods of both programming computer-readable media to
perform particular steps and executing the steps.
[0109] The methods disclosed herein include and encompass, in
addition to methods of practicing the present technology (e.g.,
methods of making and using the disclosed devices and systems),
methods of instructing others to practice the present technology.
For example, a method in accordance with a particular embodiment
includes locating a distal end portion of an elongate shaft within
or otherwise proximate to a vessel or lumen of a human patient,
partially decoupling a neuromodulation element from the distal end
portion, expanding a support structure of the neuromodulation
element radially outward relative to a central longitudinal axis of
the vessel or lumen so as to move a therapeutic element carried by
the support structure toward a wall of the vessel or lumen,
modulating one or more nerves of the patient using the therapeutic
element while the neuromodulation element is partially decoupled
from the distal end portion, conveying energy toward the
therapeutic element via a flexible tether extending between the
distal end portion and the neuromodulation element while modulating
the one or more nerves. A method in accordance with another
embodiment includes instructing such a method.
[0110] 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.
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