U.S. patent application number 15/092442 was filed with the patent office on 2017-03-23 for intravascular tissue disruption.
The applicant listed for this patent is Jeffery A. KROLIK, Suresh PAI, Amr SALAHIEH, Tom SAUL, Alan SCHAER, John SPIRIDIGLIOZZI. Invention is credited to Jeffery A. KROLIK, Suresh PAI, Amr SALAHIEH, Tom SAUL, Alan SCHAER, John SPIRIDIGLIOZZI.
Application Number | 20170080184 15/092442 |
Document ID | / |
Family ID | 44673869 |
Filed Date | 2017-03-23 |
United States Patent
Application |
20170080184 |
Kind Code |
A1 |
SALAHIEH; Amr ; et
al. |
March 23, 2017 |
INTRAVASCULAR TISSUE DISRUPTION
Abstract
Disrupting tissue and devices and systems for disrupting tissue.
The disclosure describes ways to deliver moieties to a target
tissue, where the target tissue in general is not at the point of
introduction, in such a way that minimal damage is produced in the
tissue at the point of introduction. In some embodiments this is
accomplished by jetting fluid at high velocity into the target
tissue. The disclosure further describes novel agents deliverable
in such systems for use in remodeling tissues. Some of these agents
comprise a liquid while others do not. Additionally, although not
specifically described in detail much of the disclosure may
additionally be used in the delivery of therapeutic drugs.
Inventors: |
SALAHIEH; Amr; (Saratoga,
CA) ; SCHAER; Alan; (San Jose, CA) ; KROLIK;
Jeffery A.; (Campbell, CA) ; SPIRIDIGLIOZZI;
John; (Boston, MA) ; PAI; Suresh; (Mountain
View, CA) ; SAUL; Tom; (Moss Beach, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
SALAHIEH; Amr
SCHAER; Alan
KROLIK; Jeffery A.
SPIRIDIGLIOZZI; John
PAI; Suresh
SAUL; Tom |
Saratoga
San Jose
Campbell
Boston
Mountain View
Moss Beach |
CA
CA
CA
MA
CA
CA |
US
US
US
US
US
US |
|
|
Family ID: |
44673869 |
Appl. No.: |
15/092442 |
Filed: |
April 6, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13351962 |
Jan 17, 2012 |
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15092442 |
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13071436 |
Mar 24, 2011 |
8840601 |
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13351962 |
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61317231 |
Mar 24, 2010 |
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61324461 |
Apr 15, 2010 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61M 25/008 20130101;
A61M 2202/0468 20130101; A61M 25/1002 20130101; A61M 2025/0681
20130101; A61M 25/0068 20130101; A61M 25/04 20130101; A61M 25/0054
20130101; A61M 2210/12 20130101; A61M 25/0071 20130101; A61M 25/09
20130101; A61M 2025/0079 20130101; A61M 25/0075 20130101; A61M
2025/1097 20130101; A61M 2202/0484 20130101; A61M 2202/20 20130101;
A61M 2025/105 20130101; A61M 2202/049 20130101; A61M 25/0097
20130101; A61M 2025/0096 20130101; A61M 25/0082 20130101; A61M
25/0074 20130101 |
International
Class: |
A61M 25/00 20060101
A61M025/00; A61M 25/09 20060101 A61M025/09 |
Claims
1.-7. (canceled)
8. A method for treating a human patient with diagnosed
hypertension, the method comprising: positioning an elongate
delivery member having a distal fluid delivery region within a
renal blood vessel and proximate to renal nerves of the patient;
transforming the fluid delivery region from a low-profile delivery
configuration to an expanded treatment configuration, wherein the
fluid delivery region comprises a plurality of tubular elements,
and wherein, in the expanded treatment configuration, each tubular
element is bent along a bending region of the respective tubular
element to position a portion of the individual tubular elements in
contact with a wall of the renal blood vessel; delivering a
neuromodulatory fluid via one or more of the tubular elements to
attenuate or block neural signaling along the renal nerves; and
removing the elongate delivery member and fluid delivery region
from the patient after delivering the neuromodulatory fluid to
conclude the procedure.
9. The method of claim 8 wherein positioning the elongate delivery
member having the distal fluid delivery region within a renal blood
vessel comprises intravascularly delivering the elongate delivery
member and fluid delivery region through an abdominal aorta to a
renal artery of the patient.
10. The method of claim 8 wherein positioning the elongate delivery
member having the distal fluid delivery region within a renal blood
vessel comprises delivering the elongate delivery member to the
renal blood vessel via a guidewire.
11. The method of claim 8 wherein the fluid delivery region of the
elongate delivery member comprises a control member axially movable
with respect to the elongate delivery member, and wherein distal
and proximal end regions of the tubular elements are fixed to the
control member, and further wherein: transforming the fluid
delivery region from a low-profile delivery configuration to an
expanded treatment configuration comprises actuating the control
member in a proximal direction to urge the distal and proximal end
regions of the individual tubular elements toward each other,
thereby causing the tubular elements to bend along the
corresponding bending regions outward away from the control member
and toward the wall of the renal blood vessel.
12. The method of claim 11, further comprising actuating the
control member in a distal direction after delivering the
neuromodulatory fluid to urge the distal and proximal end regions
of the individual tubular elements away from each other, thereby
transforming the fluid delivery region from the expanded treatment
configuration back to the low-profile delivery configuration before
removing the elongate delivery member and fluid delivery region
from the patient.
13. The method of claim 8 wherein the tubular elements each include
one or more ports for delivery of the neuromodulatory fluid
therethrough, and wherein each tubular element is in fluid
communication with a fluid source configured to store the
neuromodulatory fluid.
14. The method of claim 13 wherein, when the fluid delivery region
is in the expanded treatment configuration, each port is in contact
with or facing the wall of the renal blood vessel.
15. The method of claim 13 wherein: when the fluid delivery region
is in the treatment configuration, each of the ports faces in a
direction different from the direction it faces in when the fluid
delivery region is in the delivery configuration.
16. The method of claim 13 wherein delivering a neuromodulatory
fluid via one or more of the tubular elements to attenuate or block
neural signaling along the renal nerves comprises delivering the
neuromodulatory fluid simultaneously through the ports.
17. The method of claim 8 wherein delivering the neuromodulatory
fluid to attenuate or block neural signaling along the renal nerves
results in a therapeutically beneficial reduction in one or more
symptoms associated with the hypertension of the patient.
18. The method of claim 8 wherein delivering a neuromodulatory
fluid to attenuate or block neural signaling along the renal nerves
comprises delivering the neuromodulatory fluid to at least
partially ablate the renal nerves.
19. The method of claim 8 wherein delivering a neuromodulatory
fluid to attenuate or block neural signaling along the renal nerves
comprises delivering the neuromodulatory fluid to tissue external
to the renal blood vessel of the patient and in contact with or
adjacent to the renal nerves.
20. The method of claim 8 wherein delivering a neuromodulatory
fluid to attenuate or block neural signaling along the renal nerves
comprises delivering alcohol.
21. The method of claim 8 wherein delivering a neuromodulatory
fluid to attenuate or block neural signaling along the renal nerves
comprises delivering a neurotoxin.
22. The method of claim 8 wherein delivering a neuromodulatory
fluid to attenuate or block neural signaling along the renal nerves
comprises delivering botulinum toxin.
23. The method of claim 8 wherein the renal blood vessel is a first
renal artery and the renal nerves are first renal nerves, and
wherein the method further comprises: after delivering the
neuromodulatory fluid to attenuate or block neural signaling along
the first renal nerves, introducing the elongate delivery member to
a second renal artery of the patent and proximate to second renal
nerves; delivering the neuromodulatory fluid via one or more of the
tubular elements to attenuate or block neural signaling along the
second renal nerves; and after delivering the neuromodulatory fluid
to the second renal nerves, removing the elongate delivery member
and fluid delivery region from the patient to conclude the
procedure.
24. The method of claim 8 wherein, when the fluid delivery region
is in the expanded treatment configuration, it does not occlude the
renal blood vessel.
25. An apparatus for controllably releasing fluid within a
hypertensive human patient, the apparatus comprising: an elongate
shaft having a distal portion configured for intravascular
placement within a renal artery of the patient; and a fluid
delivery assembly including a plurality of tubular elements at the
distal portion of the catheter, wherein the fluid delivery assembly
is selectively transformable between a low-profile, delivery
configuration and a deployed configuration sized to fit within the
renal artery of the patient, wherein, when the fluid delivery
assembly is in the delivery configuration, the tubular elements are
generally straight and in alignment with a longitudinal axis of the
elongate shaft, wherein, when the fluid delivery assembly is in the
deployed configuration, the assembly is arranged in a basket-like
shape adapted to allow blood to flow therethrough and the tubular
elements are each bent outwardly away from the longitudinal axis
such that a portion of each tubular element is in apposition with a
wall of the renal artery; and wherein each tubular element
comprises a fluid delivery aperture and is configured when the
fluid delivery assembly is in the deployed configuration to deliver
a fluid agent via the respective aperture to target renal nerves of
the patient in an amount sufficient to modulate neural function of
the targeted renal nerves.
26. The apparatus of claim 25 wherein the tubular elements are
composed of nitinol.
27. The apparatus of claim 25 wherein the distal portion of the
elongate shaft is configured for intravascular placement within the
renal artery over a guidewire.
28. The apparatus of claim 25 wherein each of the plurality of
fluid delivery apertures is adapted to be selectively addressable
to regulate a volume of the fluid agent delivered via the
respective fluid delivery apertures.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. application Ser.
No. 13/351,962, filed Jan. 17, 2012; which is a continuation of
U.S. application Ser. No. 13/071,436, filed Mar. 24, 2011, now U.S.
Pat. No. 8,840,601; which claims the benefit of U.S. Provisional
Application No. 61/317,231, filed Mar. 24, 2010, and U.S.
Provisional Application No. 61/324,461, filed Apr. 15, 2010, the
disclosures of which are incorporated herein by reference in their
entirety.
BACKGROUND OF THE INVENTION
[0002] Various treatments to bodily tissue have been attempted.
Devices that can deliver a fluid from a distal end port of a
catheter have been described. Devices have been described that have
a valve at a distal port that allows fluid to flow through the
valve in an open configuration and prevents fluid from flowing
through the valve in a closed configuration. Devices have also been
described that can create microfluidic pulsed jets at the distal
end of a catheter. Additionally, intravascular devices that include
elements that pierce lumen walls can be deployed within a lumen and
deliver medication into a lumen wall. Some devices have a plurality
of delivery ports through which fluids are delivered
simultaneously. These devices and methods of use have one or more
shortcomings for which the disclosure herein compensates.
SUMMARY OF THE INVENTION
[0003] One aspect of the disclosure is a method of controlling the
delivery of fluid from a medical delivery device, comprising: a
medical device comprising a distal delivery region comprising a
plurality of fluid controls; and selectively regulating the flow of
a fluid through the plurality of fluid controls. In some
embodiments selectively regulating comprises allowing the fluid to
be delivered from a first fluid control while minimizing the fluid
that is delivered from a second fluid control. In some embodiments
selectively regulating comprises increasing the flow of fluid from
a first fluid control without increasing the flow of fluid through
a second fluid control. In some embodiments selectively regulating
comprises increasing the fluid flow from a first fluid control a
first amount and increasing the flow of fluid from a second fluid
control a second amount, wherein the first amount is different than
the second amount. In some embodiments selectively regulating
comprising moving a first fluid control from a closed configuration
to an open configuration without moving a second fluid control from
a closed configuration to an open configuration. Moving the first
control to the open configuration can comprise moving a first valve
element with a first aperture therein relative to a second valve
element with a second aperture therein until the apertures are in
alignment. Moving the first fluid control to the open configuration
can cause the fluid to flow from the first control at a high
velocity, while the fluid flows out of the second fluid control at
a low velocity. In some embodiments selectively regulating
comprises flowing the fluid out of a first fluid control at a high
velocity and flowing the fluid out of a second fluid control at a
low velocity.
[0004] One aspect of the disclosure is a method of regulating the
volume of a fluid delivered from a medical device, comprising: a
medical device comprising a distal delivery region comprising a
fluid control in communication with a fluid source, wherein the
fluid control comprises a first control element with a first
aperture therein and a second control element with a second
aperture therein; positioning the distal delivery region near a
target location within a patient; and regulating the volume of
fluid released from the fluid control by moving the apertures into
alignment to increase the flow of the fluid through the fluid
control. In some embodiments the regulating step occurs
independently of transience generated at a fluid pressure source.
In some embodiments the fluid source is disposed external to the
patient, further comprising maintaining a substantially constant
pressure at the fluid source. The method can further comprise
varying the fluid velocity at the fluid control to regulate the
volume of fluid released. In some embodiments regulating the volume
of fluid released further comprises moving the apertures out of
alignment to decrease the flow of fluid out of the fluid control.
In some embodiments the first control element comprises a first
tubular member and the second control element comprises a second
tubular member disposed within the first tubular member, and
wherein moving the apertures into alignment comprises moving the
first tubular member relative to the second tubular member to
thereby move the first aperture relative to the second aperture.
Moving the first tubular member relative to the second tubular
member can comprise at least one of axial movement and rotational
movement.
[0005] One aspect of the disclosure is a method of periluminal
tissue damage, comprising positioning a delivery device within a
lumen without piercing the lumen wall; delivering a fluid agent
from the delivery device through the lumen wall; and damaging
tissue peripheral to the lumen wall with the fluid agent. In some
embodiments the lumen wall comprises an intimal layer, and wherein
the damaging step comprises damaging nerve cells peripheral to the
intimal layer of the lumen wall. Damaging can comprise damaging
nerves cells while minimally damaging tissue in the intimal layer
of the vessel wall. The lumen wall can comprise a medial layer, and
wherein damaging comprises damaging tissue within the medial layer.
Damaging tissue can comprise damaging cells in at least one of a
medial layer of the lumen and nerve cells disposed within the
adventitial layer. A damage cross section can increases as the
radial distance from the intimal layer increases.
[0006] In some embodiments the delivery device comprises a first
fluid control and a second fluid control, wherein delivering
comprises delivering the fluid agent from the first fluid control
to create a first damage region, and delivering the fluid agent
from the second fluid control creates a second damage region,
wherein portions of the first and second regions overlap. In some
embodiments damaging comprises damaging tissue with the direct
mechanical interaction of the fluid. In some embodiments damaging
is caused by chemical interactions with the fluid, such as a
hypotonic, a hypertonic fluid, a fluid that self-heats on
interaction with tissue, a fluid that has a pH significantly
different from the pH of the tissue, a fluid that comprises
material toxic to the tissue, a fluid that comprises material toxic
to a particular tissue, a fluid that comprises material which
becomes toxic on interaction with the tissue, or a fluid that
comprises material which is capable of absorbing energy delivered
from a source external to the body.
[0007] In some embodiments delivering a fluid agent from the
delivery device through the lumen wall comprises delivering the
fluid agent towards neural tissue peripheral to an intimal layer of
the lumen. In some embodiments damaging comprises damaging renal
nerve tissue peripheral to a lumen of a renal artery. In some
embodiments damaging renal nerve tissue reduces hypertension.
[0008] One aspect of the disclosure is an apparatus for releasing
fluid within a patient's body, comprising: an elongate member
comprising a distal region comprising a plurality of fluid
controls, a lumen extending through the distal region and in fluid
communication with the plurality of fluid controls, wherein the
lumen is adapted to be in fluid communication with a fluid source,
wherein each of the plurality of fluid controls is adapted to be
selectively addressable to regulate the volume of a fluid that is
released from the lumen and out the plurality of fluid
controls.
[0009] In some embodiments the fluid control has a closed
configuration and an open configuration, wherein in the closed
configuration a substantially smaller volume of fluid, such as no
fluid, is allowed to be released out of the fluid control than in
the open configuration. In the open configuration the fluid control
can be adapted to release the fluid at high velocity. In some
embodiments the distal region comprises a plurality of fluid
controls in fluid communication with the lumen, each fluid control
has open and closed configurations, and wherein each fluid control
is adapted to regulate the volume of fluid that is released from
the fluid control when the fluid is delivered at high velocity. The
plurality of fluid controls can be adapted to be individually
opened. In some embodiments the fluid control is adapted to be in
fluid communication with a fluid source maintained at a
substantially constant pressure. The fluid control can control the
volume of fluid that is released from the fluid control while the
fluid source is maintained at the substantially constant
pressure.
[0010] One aspect of the disclosure is an apparatus for
controllably releasing fluid within a patient's body, comprising: a
first tubular element with a first aperture therein; a second
tubular element with a second aperture therein, wherein the second
tubular element is disposed within the first tubular element and
movable relative to the first tubular element, wherein the second
tubular element has a lumen therethrough adapted to be in fluid
communication with a fluid source, and wherein the apertures have
an aligned configuration that allows a fluid to pass from the lumen
through the first and second apertures. In some embodiments the
apertures have an aligned configuration that allows a fluid to pass
through the apertures at a high velocity. In some embodiments the
second aperture has a smaller maximum dimension than a maximum
dimension of the first aperture. In some embodiments the apparatus
further comprises a fluid source maintained at substantially a
constant pressure. The apertures can be adapted to release a fluid
therethrough at high velocity. The apertures can have an aligned
configuration that allows fluid to pass therethrough when the fluid
source is maintained at a substantially constant first pressure
during a first delivery cycle and when the fluid source is
maintained at a substantially constant second pressure during a
second delivery cycle, wherein the first and second pressure are
different. In some embodiments the first tubular element has a
deformed treatment configuration wherein at least a portion of the
first tubular element is adapted to engage a lumen wall in which it
is positioned. The deformed treatment configuration can be
substantially spiral-shaped. The apparatus can further comprise an
expandable element that is adapted to deform the first tubular
element into contact with the lumen wall. The expandable element
can comprise a balloon. The expandable element can be moveable
relative to the first tubular element to cause the first tubular
element to be deformed into the treatment configuration. In some
embodiments the apparatus further comprises a piercing element in
fluid communication with the first aperture and extending from the
first aperture, wherein the piercing element is adapted to pierce
tissue and allow for the fluid to flow from the aperture and out of
the piercing element. In some embodiments the apertures have a
non-aligned configuration that is adapted to allow fluid to flow
therethrough at a low velocity.
[0011] One aspect of the disclosure is an apparatus for
controllably releasing fluid within a patient's body, comprising:
an elongate member comprising a distal end, a proximal end, and a
therapy portion in between the ends; the therapy portion comprises
a plurality of expandable elongate elements, each with a delivery
configuration and a treatment configuration, wherein each of the
plurality of expandable elongate elements comprises a fluid
control, and in the delivery configuration the control faces a
first direction and in the treatment configuration the control
faces a second direction different than first direction. In some
embodiments the second direction is generally orthogonal to a
longitudinal axis of the elongate member. In some embodiments the
first direction is substantially parallel to a longitudinal axis of
the elongate member. In some embodiments the expandable elongate
elements are tubular elements, and wherein the fluid controls are
provided by removing sections from the tubular elements. In some
embodiments the fluid controls are proximal to distal ends of the
elongate elements. In some embodiments the expandable elongate
elements are adapted to preferentially bend in the region of the
fluid ports in the treatment configurations. In some embodiments
the expandable elongate elements are self-expanding. In some
embodiments the expandable elongate elements are actuatable.
INCORPORATION BY REFERENCE
[0012] All publications and patent applications mentioned in this
specification are herein incorporated by reference to the same
extent as if each individual publication or patent application was
specifically and individually indicated to be incorporated by
reference.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] A better understanding of the features and advantages of the
present disclosure will be obtained by reference to the following
detailed description that sets forth illustrative embodiments, in
which the principles of the disclosure are utilized, and the
accompanying drawings of which:
[0014] FIG. 1 illustrates an exemplary delivery system adapted to
remodel tissue.
[0015] FIG. 2 illustrates an exemplary delivery system including a
fluid system.
[0016] FIGS. 3, 4, 5 and 6 illustrate an exemplary embodiment of a
delivery system incorporating a fluid system and a plurality of
expandable tubular elements.
[0017] FIGS. 7, 8, 9 and 10 illustrate an exemplary method of
remodeling renal nerves surrounding a renal artery.
[0018] FIG. 11 illustrates an exemplary reconfigurable distal
delivery region that is an extension of an elongate delivery
member.
[0019] FIG. 12 illustrates a distal delivery region including an
elongate tubular element that has a spiral procedural
configuration.
[0020] FIG. 13 illustrates a distal delivery region including first
and second tubular elements that have spiral procedural
configurations.
[0021] FIG. 14 illustrates an exemplary portion of a distal
delivery region, wherein a spiral element comprises two spring
elements on either side of a valve.
[0022] FIGS. 15 and 16 illustrate perspective and end views,
respectively, of an exemplary embodiment of the distal delivery
region that includes a tubular element, and includes a plurality of
penetrating remodeling elements.
[0023] FIGS. 17 and 18 illustrate exemplary embodiments of distal
delivery region including a plurality of expandable tubular
elements.
[0024] FIGS. 19 and 20 illustrate exemplary distal delivery regions
incorporating expandable balloons.
[0025] FIGS. 21, 22, 23 and 24 illustrate distal delivery regions
that include incorporates one or more apertures on outer and inner
tubular members.
[0026] FIGS. 25 and 26 illustrate a spiraled distal delivery region
expanded in a renal artery.
[0027] FIGS. 27, 28, 29, 30, 31 and 32 illustrate exemplary needle
valves that can be activated from a proximal end of the delivery
system.
[0028] FIGS. 33, 34 and 35 illustrate an exemplary embodiment of a
metering valve configuration.
[0029] FIGS. 36 and 37 illustrate a distal delivery region
including penetrating remodeling agents deployed within a section
of a renal artery.
[0030] FIG. 38 illustrates an exemplary distal delivery region
incorporating a remodeling element that is a needle with a helical
configuration.
[0031] FIG. 39 illustrate a representation of the fluidic
performance of the exemplary valve shown in FIG. 42.
[0032] FIG. 40 is a figurative representation of the delivery
system in terms of its resistive fluidic characteristics.
[0033] FIG. 41 illustrates a representation of the expected outflow
rate as a function d given the resistance characteristics
represented in FIG. 40 and a constant pressure supply.
[0034] FIG. 42 provides a figurative representation of a delivery
system incorporating a distal fluid control configured as a shuttle
valve.
[0035] FIG. 43 illustrates the system of FIG. 39, wherein the
shuttle valve is replaced by a needle valve.
[0036] FIG. 44 illustrates an exemplary distal delivery region
wherein a fluid or gas may be used to eject a component capable of
external excitation or alternatively a component which upon
ejection springs into a shape different than its delivery shape and
in so doing damages tissue in its vicinity, thereby causing tissue
remodeling.
[0037] FIG. 45 illustrates a distal delivery region comprising
slicing hooks or simple blades which cut tissue on being
advanced.
[0038] FIG. 46 illustrates an exemplary distal delivery region
comprising an atherectomy blade that can be spun to facilitate the
requisite tissue remodeling.
[0039] FIG. 47 illustrates an exemplary distal delivery region
similar to that in FIG. 36.
DETAILED DESCRIPTION OF THE INVENTION
[0040] The disclosure herein relates generally to disrupting tissue
and devices and systems for disrupting tissue. More specifically,
the disclosure describes ways to deliver moieties to a target
tissue, where the target tissue in general is not at the point of
introduction, in such a way that minimal damage is produced in the
tissue at the point of introduction. In some embodiments this is
accomplished by jetting fluid at high velocity into the target
tissue. The disclosure further describes novel agents deliverable
in such systems for use in remodeling tissues. Some of these agents
comprise a liquid while others do not. Additionally, although not
specifically described in detail much of the disclosure may
additionally be used in the delivery of therapeutic drugs.
[0041] Procedures that allow for the disruption or remodeling of
tissues peripheral to body lumens, particularly while minimizing
disruption to the inner surface of the body lumen and often the
tissues comprising the wall of the body lumen are advantageous in a
number of medical procedures. Such procedures include but are not
limited to: disruption of nerves in the medial and adventitial
tissue surrounding body lumens such as arteries and veins,
including the renal arteries and pulmonary arteries and veins,
disruption of cancerous tissues surrounding body lumens such as the
esophagus for the treatment of various cancers, and urethra for
treatment of various cancers such as prostate cancer. Such
remodeling treatments may additionally be used to shrink tissues
such as sphincters of the bowel, urethra, stomach, or intestines,
amongst others. Further advantage is obtained when such procedures
can be achieved percutaneously, which include endovascular, or
minimally invasive delivery of the apparatus required to facilitate
the procedure. Additionally, the ability to refine or continue the
remodeling of the target tissue after the completion of the
percutaneous or minimally invasive procedure has advantages where
the outcome of the initial procedure is unclear for some period of
time following the procedure or where some level of healing
obviates the damage and further remodeling is required. The various
configurations of the apparatus and associated methods described
below facilitate such procedures.
[0042] Although the devices described herein are particularly
useful for delivering agents to tissues peripheral to body lumens
from within the body lumen, they also will have application in the
delivery of agents via pathways and/or in locations independent of
body lumens. Such uses include treatment of tumor such as those of
the liver or lung.
[0043] The embodiments described herein associated with the
delivery of moieties comprising fluids provide one or more of the
following advantages over that which has been described: improved
ways for controlling the consistency in dose and or velocity for
multi jet systems across the jets; ways for controlling the dose;
use of a constant pressure source while achieving metered bolus
delivery while maintaining high initial fluid velocity and control
of fluid velocity; and minimizing leakage of delivered material
while not in delivery cycle. Additionally, in some embodiments the
delivery of the fluid jets is controlled in a distal region of the
delivery system, thereby minimizing negative effects of system
capacitance and long fluid channels on rate at which peak fluid
velocity is attained at an exit aperture and delivered dosage.
Additionally, damage that is caused by moving a fluid jet while it
is constantly activated and slicing large areas of tissue may be
minimized by minimizing the duration of on cycles.
[0044] In some embodiments mechanical disruption of the tissue is
effected by high velocity fluid jets situated at or near the target
site. The jets may be located at the inner surface of a body lumen
and directed thru the body lumen towards the target tissue. The
jets, as they enter the body lumen, are highly focused and
therefore interact with a small area of the adjoining lumen wall
and volume of adjoining tissue. As the jet passes through the lumen
wall, the fluid interacts with the tissue and is spread over a
larger volume of tissue, disrupting an increasingly larger area of
tissue. However, as the area of interaction is increased the
fluid's direct interaction is dissipated and so is the associated
damage. The direct interaction of the fluid may be to cut,
separate, or swell. In some embodiments the jet may be moved to
create a slice in adjoining tissue. The jets may additionally be
designed such that the shape of the injected fluid volume would be
caused to spread in one or two directions normal to the forward
direction as it enters the tissue.
[0045] Alternatively, in some embodiments, the source of the high
velocity jets may be passed through the inner surface of the lumen
wall and into the wall of the body lumen, or the source of the high
velocity jets may be passed completely through the body lumen into
the tissue surrounding the body wall. The apparatus may also be
configured such that combinations of these approaches may be
performed.
[0046] In some embodiments the fluid delivered via the high
velocity injection system is an ablative media such as one of those
described below. An ablative material may be delivered to the
target tissue without passing any portion of the delivery structure
through the wall of the body lumen. Since needles or other
structures capable of fraying or tearing the body lumen are not
passing through the body lumen, no motions associated with the
delivery of the delivery structure or those associated with
movement of the patient can cause damage to the body lumen. This
may be especially important where the body lumen is frail or where
a tear in the body lumen could cause uncontrollable bleeding.
Additionally, the cross section of a jet will be smaller than a
delivery needle of comparable lumen size.
[0047] Some moieties or agents that can necrose tissue, capable of
delivery in the fashion described, are hypertonic or hypotonic
solutions which induce drying or bursting of cells. In the case of
hypertonic, simple salt solutions and alcohols may be used to these
ends. ETOH and mixtures of ETOH and H.sub.2O.sub.2 are particularly
useful as such ablative fluids. The H.sub.2O.sub.2 in this mixture
brings about additional damage as a result of oxidative stress.
[0048] Another set of agents useful for necrosing tissues are those
which generate heat and can be delivered in the fashion so far
described. These materials, upon interaction with each other or the
environment of the target tissue, generate heat as a result of an
ensuing chemical reaction or solubilization. Examples of materials
which when contacted with water in the target tissue begin a
reaction which is exothermic include: iron particles, exothermic
salts. An exemplary, but incomplete, lists of salts which can be
used to this purpose are CaCl.sub.2, CaSO.sub.4, MgSO.sub.4,
K.sub.2CO.sub.3, Na.sub.2SO.sub.4. These salts when delivered as a
suspension in a non-aqueous carrier, such as a light oil or alcohol
amongst others, generate heat upon rehydration. When appropriate
masses of salt are delivered to a small volume of tissue the heat
generated from the hydration of the salt and the consumption of
water in the local environment will both necrose the tissues
adjacent to the delivery zone. The conformation of the salts as
delivered for this purpose can further add to the heat generating
capability. For example, the salts can be finely divided such that
surface to volume ratio is increased and therefore the rate of
rehydration and heat generation is enhanced. Finely divided salt
particles can range in size from about 0.1 to about 100 microns.
Especially useful for this purpose would be the suspensions of
nanoparticle sized particles of the salts in which the surface to
volume ratio is even further enhanced. These nanoparticles having a
size range of 10 nm to 100 nm. Nanoparticles of NaCl, delivered in
a light oil or reagent grade alcohol, upon delivery to a target
tissue will upon solubilization create both an endothermic reaction
and a hypertonic local environment. The oxidation of iron particles
provides another system which will behave in a fashion similar to
that just described for the exothermic salts. Any such system which
relies on such reactions and incorporates a particle as part of the
delivered material will behave in much the same fashion as the
salts and iron particles described above and will also benefit from
an increase in surface to volume ratio such as that associated with
decreasing the size from micron to nano dimensions. Other examples
of materials which may be mixed at the target location include
acids and bases such as: HCl and NaOH, or weak acids and metals
such as HCl and Mg, catalyzed polymerization reactions such as that
for methyl methacrylate resins, many others can be chosen form,
which are familiar to those skilled in the art. An acid or base may
also be delivered independently of the other. The use of acetic
acid is such an example which has a demonstrated usefulness in
ablating tumors.
[0049] Yet another set of agents useful for tissue remodeling,
where the target tissue are specifically nerve tissues, are nerve
toxins such as the botulinun neurotoxins or capsacin. Many other
irreversibly acting nerve toxins, known to those familiar with the
art, may be delivered in this fashion.
[0050] In other circumstances blood or blood products may used as
an agent. In this circumstance the blood may be separated and only
plasma used, or alternatively the platelets and cellular material
may be used. When preparations containing cells are used the
preparation may be homogenized to break down the cell structures.
The preparation may also be thinned with sodium citrate and or
heparin or other anti clotting agents may be added. In yet other
circumstances enzymes including neurolytic and necrotizing may be
used. Detergents may also be used independently or in combination
with any of the fluids described herein.
[0051] In some instances it may be advantages for the agent to be
deliverable in a low viscosity form and then on interaction with
the environment on the target tissue increases in viscosity
possibly becoming a gel. An acid solution comprising collagen, on
introduction to the roughly normal pH of a target tissue, will
polymerize forming a resorbable gel like material which may
additionally comprise nanoparticles or other materials described
herein.
[0052] In some embodiments disruption or remodeling is achieved by
an externally induced interaction between a material delivered to
the target tissue and the target tissue. Such materials are
configured to be delivered to the target site by percutaneous or
minimally invasive procedures. Upon completion of material
delivery, the material is induced to facilitate the remodeling by
an energy field which is created at a site external to the body and
directed to the target site by non-invasive means. The induced
interactions may be creation or release of toxins or necrosing
agents, the generation of heat, mechanical disruption or any other
means which eventuates the necroses or loss in functionality of
cells in the target tissue. These materials may additionally
contain agents to enhance their contrast when viewed by
radiographic, acoustic, or MRI means. It should be noted that these
materials may also be energized from energy sources delivered
minimally invasively or percutaneous to locations near the target
tissue.
[0053] One set of materials which may be used for the generation of
heat are induced to heat by the application of acoustic energy.
Examples of such materials include ethyl vinyl acetate, silicone,
urethanes and other materials known in the art.
[0054] Yet another set of materials that can be induced to generate
heat are those capable of absorbing electromagnetic energy, in
particular changing magnetic fields (inductive heating). Examples
of such materials include ferrites and other iron bearing materials
and materials containing Nickel. As an example, heating occurs when
an alternating, uniformly high flux density magnetic field induces
an alternating current in a lossy conductor. A gapped toroid can
generate such a magnetic field. A solenoid's magnetic field can
produce the required magnetic field for inductive heating of
discrete particles. In addition to heating particles that have been
distributed in the lumen of the body, the external magnetic field
could also be used to couple energy into a catheter in place of
electrical conductors. The external magnetic field could also be
used to actuate or position features of the catheter in place of
mechanisms (e.g., pull wires etc.).
[0055] Yet another use for a magnetic field would be the physical
manipulation of a magnetic dipole (or multitude thereof). One use
of such a manipulation would be to move a magnetic particle to a
desired location in order to deliver a payload. Another use of such
a manipulation would be to move a magnetic particle in such a
fashion to be disruptive to the surrounding tissue. A means for
inducing said magnetic manipulation could be through the use of a
3-dimensional (3D) array of solenoids whose magnetic fields
intersect and form a magnetic field vector that manipulates a
magnetic particle(s).
[0056] In another class of materials the necrosing agent is
designed to be released or to convert as a function of energy
absorption.
[0057] The fluid delivery means described herein may be used for
the delivery of therapeutic agents in addition to ablative agents.
One such therapeutic agent is Taxol, which may be used to minimize
post treatment stenosis. Hypertensive drugs may also be delivered
in this fashion.
[0058] Any of these materials can be configured for delivery by the
mechanisms described above or by more conventional means commonly
practiced today, such as the use of simple injection from a needle
or system of needles delivered to the body lumen in the vicinity of
the target tissue. In such systems the final spacial geometry of
the delivered material may be important. Such a situation exists
for example with regard to the denervation or necrosing of
adventitial and medial tissue surrounding the renal artery for the
treatment of hypertension. In this situation it can be advantages
to deliver the material in a spiral pattern about the vessel in the
adventitial tissue surrounding the vessel.
[0059] In some methods of use, an agent can be delivered to renal
nerve tissue to disrupt the neural tissue to treat hypertension.
The treatment of hypertension can be accomplished by modulating of
neural signal transmission along the renal nerve. Modulation
includes activation of neural activity, suppression of neural
activity, denervation of tissue, ablation of tissue, etc. The
relationship between renal nerve signal transmission and
hypertension may be found in, for example, U.S. Pat. No. 6,978,174,
U.S. Pat. No. 7,162,303, U.S. Pat. No. 7,617,005, U.S. Pat. No.
7,620,451, U.S. Pat. No. 7,653,438, U.S. Pat. No. 7,756,583, U.S.
Pat. No. 7,853,333, and U.S. Pub. No. 2006/0041277, U.S. Pub. No.
2006/0206150, U.S. Pub. No. 2006/0212076, U.S. Pub. No.
2006/0212078, U.S. Pub. No. 2006/0265014, U.S. Pub. No.
2006/0265015, U.S. Pub. No. U.S. Pub. No. 2006/0271111, U.S. Pub.
No. 2006/0276852, U.S. Pub. No. 2007/0129760, and U.S. Pub. No.
2007/0135875, the complete disclosures of which are incorporated
herein by reference. The systems and methods of use herein can be
used to disrupt the tissue to modulate neural transmission along a
renal nerve in order to treat hypertension.
[0060] The above materials may be delivered as solutions with a
wide range of viscosities or be viscous gels. The materials either
ablative or otherwise so far described may contain contrast agents
and or anesthetics. Additionally, materials may be designed such
that on interacting with the target site the viscosity increases or
the material gels, or mixed on delivery such that they the
viscosity increases or the material gels at the target site.
Alternatively the materials can be formed as a solid designed to be
projected into the target tissue thru the body lumen wall and into
the target tissue. Such a mechanism could be driven by high
velocity fluids, gases, or by mechanical means such as springs.
[0061] Any of the above materials can be combined such that they
possess any of the following characteristics to fit the particular
application: bioresorbable, biocompatible, or designed to remain in
place for extended periods of time.
[0062] Agents which may be added to enhance contrast for imaging
procedures will be dependent on the particular imaging procedure.
Examples of such materials which enhance MRI imaging are
Gadolinium, magnetic materials especially those containing nickel,
and or ferrites. Examples of those for use with acoustical
procedures are silicones, metal or metal oxide particles, amongst
others known in the art. Examples of such materials useful for
radiological procedures are barium sulfate, tantalum powder, or the
like. These examples are not exhaustive and many alternatives,
familiar to those skilled in the art may be chosen.
[0063] FIG. 1 illustrates an exemplary delivery system adapted to
disrupt tissue peripheral to a body lumen. Delivery system 10
includes handle 11 and elongate delivery member 13. Associated with
a distal portion of elongate member 13 is distal delivery region
14. Distal delivery region 14 includes one or more fluid controls
16. Handle 11 includes at least one delivery member actuation
element 12 (two shown), and at least one fluid control actuation
element 15 (two shown). Delivery member actuation element 12 can be
adapted to steer delivery member 13, including distal delivery
region 14, to a target location within the body. Delivery member
actuation element 12 can also be adapted to reconfigure distal
delivery region 14 between a delivery configuration and one or more
procedural configurations. Fluid control actuation element 15 is
adapted to actuate fluid controls 16 to effect peripheral tissue
remodeling.
[0064] FIG. 2 illustrates an exemplary delivery system with a fluid
system. Although system 20 is represented as an assembly of
components separate from handle 11, fluid system 20 may be
incorporated within handle 11. Fluid system 20 includes fluid
reservoir 21 and optional additional reservoirs 22. Reservoir(s)
interface with pressure source 23 which provides the motive force
for delivering an agent to fluid controls 16 (see FIG. 1). Tissue
disruption is mediated by the delivery of an agent from the fluid
reservoirs to fluid controls 16. Fluid control actuation element 15
may alternatively be located within fluid system 20.
[0065] FIGS. 3-6 illustrate an exemplary embodiment of a delivery
system incorporating a fluid system. Although the exemplary fluid
system shown can be incorporated with any of the elongate delivery
members herein, as shown in FIG. 3 the fluid system is incorporated
into handle 11. Pressure source 23 includes a gas cartridge, such
as a CO.sub.2 cartridge, which is in fluid communication with fluid
reservoir 21, which in turn is in fluid communication with valve
38, which functions as the fluid control actuation element. In FIG.
3 delivery member actuation element 39 facilitates the
reconfiguration of distal delivery region 14 from the delivery
configuration shown in FIG. 4 to a procedural, or treatment,
configuration shown in FIG. 5. Distal delivery region 14 comprises
a plurality of expandable tubular elements 31 that are adapted to
be reconfigured from respective delivery configuration as shown in
FIG. 4 to expanded configurations shown in FIG. 5. In the delivery
configurations the tubular elements are generally straight, and in
substantial alignment with the longitudinal axis of the delivery
member 13. Distal delivery region 14 is shown comprising four
tubular elements 31 but any suitable number may be incorporated.
Tubular elements 31 may be sealed at their distal ends, and are
secured to a distal portion of outer sheath 36. Tubular elements 31
include ports 35 in fluid communication with a fluid source. In the
embodiments shown, the ports are formed by removing a portion of
the tube wall proximal to the distal ends of tubular elements 31.
The system includes control member 33 (see FIG. 5), which is
disposed within a portion of sheath 36 proximal to distal delivery
region 14. Control member 33 is axially moveable with respect to
the proximal portion of sheath 36 and is fixed to the sheath and
tubular elements 31 distal to the distal delivery region. When
control member 33 is actuated in the proximal direction, such as by
actuation of delivery member actuation element 39, the distal and
proximal ends of tubular elements 31 are urged closer together,
causing tubular elements 31 to bend at bending regions 34 radially
outward from the control member. When bent, the ports 35 are
brought into contact, or at least pointed towards the lumen wall in
which the distal delivery region is positioned. Fluid or agent can
then be delivered from the fluid source through ports 35 to disrupt
the tissue, which is described in more detail above. After the
treatment has been administered, control member 33 is advanced
distally with respect to the proximal portion of sheath 36 to move
the ends of the tubular elements away from one another,
reconfiguring the tubular elements back towards their delivery
configurations. When the tubular elements are in their expanded
configurations, ejection ports 35 are disposed in a plane
substantially normal to that of the longitudinal axis of elongate
delivery member 13. More or fewer elongate tubes can be in the
distal delivery regions. Alternatively to the configuration
depicted in FIGS. 3-6, the ports 35 can be staggered, which may be
appropriate for different tissue disruption treatments. Flexible
tubes 31 may be fabricated from any suitable flexible materials,
such as nitinol. In this embodiment control member 33 has a lumen
and thereby also provides the function of a guide wire lumen.
[0066] FIGS. 7-10 illustrate an exemplary method of remodeling of
renal nerve plexus 43 surrounding renal artery 40 of kidney 44
using the exemplary system shown in FIGS. 3-6. Although the renal
nerve plexus is depicted as two nerves for ease of representation,
the renal nerve plexus actually wraps around the renal artery.
Elongate delivery member 13 with distal delivery region 14 is
delivered from a femoral artery or other suitable location, using
known techniques, to descending aorta 41, then into renal artery
40. The delivery is facilitated by guidewire 17 which has been
previously delivered by traditional means to the renal artery.
Alternatively, for embodiments which incorporate steering
capabilities the delivery may be facilitated without the use of a
guide wire. Or in yet other alternative embodiments the delivery
may be facilitated by the use of a steerable introducer catheter
such as those described in U.S. patent application Ser. No.
12/823,049, filed Jun. 24, 2009, now U.S. Pat. No. 8,323,241, the
disclosure of which is incorporated herein by reference. Upon
delivery the distal delivery region 14 is expanded to a delivered
configuration as shown in FIG. 8 by actuating the delivery member
actuation element. In some embodiments the actuation element is
advanced distally. The pressure source control element (see element
38 in FIG. 3) is activated thereby initiating the delivery of a
dose configured as a high velocity jet of fluid 51 as indicated in
FIG. 9. Single or multiple jets may be delivered while the distal
deliver region is in any given location. The distal delivery region
may be moved to a new location by releasing (or further actuating)
tissue expansion control element 12 (see FIG. 3), which
reconfigures the distal delivery region. The distal delivery region
can then be moved to a second location, followed by actuation of
the tissue interface expansion control element 12. The volume of
tissue affected by the delivered fluid can be controlled by the
volume of each individual fluid jet, the number of jets delivered
at any given location, and the number and density of locations at
which jets are delivered. After a desired number of jets are
delivered to an appropriate number of locations, the action of the
delivered fluid will affect a large enough volume of tissue to
affect at least a portion of the renal nerve plexus, herein
described as renal nerves, passing through the affected volumes of
tissue and indicated in FIG. 10. Any of the systems described
herein can be used in the method shown in the exemplary method of
FIGS. 7-10.
[0067] FIGS. 11-19 illustrate various distal delivery regions 14.
FIG. 11 represents a reconfigurable distal delivery region which is
an extension of elongate delivery member 13. In FIG. 11 the distal
delivery region comprises an elongate tubular element in a
treatment, or expanded, configuration. In the delivery
configuration (not shown), the elongate tubular element is in a
substantially straight configuration. During delivery the distal
delivery region 14 substantially co-aligns with elongate delivery
member 13 and upon exiting a delivery catheter assumes the
configuration in FIG. 11 because of the resilient characteristics
of the material. For example, the distal delivery region can be
comprised of nitinol and utilize the superelastic property of
nitinol to self-expand when deployed from a delivery catheter. The
elongate tubular element has a generally circular or elliptical
configuration such that the contact region between the tubular
element and the lumen wall falls roughly in a plane and has an
elliptical or circular shape. Some embodiments use devices and
methods shown in co-owned U.S. patent application Ser. No.
12/823,049, filed Jun. 24, 2009, now U.S. Pat. No. 8,323,241,
wherein a tensioning element and a compression element are operated
in opposition to one another. The compression element incorporates
a laser cut pattern which collapses into the indicated shape. In
such a configuration the resultant shape and delivery system can
maintain a great degree of stiffness both along the delivery axis,
in torsion, and in maintaining the shape of the tubular element. In
FIG. 11, distal delivery region 14 also includes fluid control 16,
which includes at least one fluid jet aperture, discussed in more
detail below. When distal delivery region 14 transfers from its
delivery configuration to its procedural configuration, fluid
control 16 is urged against the lumen wall of the target tissue.
Distal delivery region 14 may be moved from position to position by
allowing it to return to its delivery configuration or in some
cases by moving it in its procedural configuration.
[0068] The tissue interface of FIG. 11, although shown with the
looped tissue interface sitting in a plane normal to the delivery
axis, may alternatively be configured such that it is in a plane
upon which the delivery axis exists. Such a configuration may be
comprised of a sinusoidal tissue interface incorporating one or
more cycles of the sinusoid. Additionally each cycle or half cycle
may fall on a different plane rotated from the previous one around
the delivery axis.
[0069] FIG. 12 illustrates a distal delivery region including an
elongate tubular element that has a spiral procedural configuration
(as shown), such that the contact regions between the tissue and
the tubular element have a spiral configuration. The device in FIG.
12 is adapted to be actuated in similar manner to the device in 11.
FIG. 13 illustrates a distal delivery region 14 including first and
second tubular elements, which are adapted to be actuated in
similar fashion to the device in FIG. 12. The elongate tubular
elements in FIG. 13 have spiral configuration when expanded, and
their contact regions with the target lumen are spiral. The
elongate tubular elements shown in FIGS. 12 and 13 include a
plurality of fluid controls 16. The expanded spiral structures of
FIGS. 12 and 13 urge the associated remodeling elements 16 into
contact with the target lumen. With a plurality of elongate
elements as in FIG. 13, forces from the plurality of tubular
elements against the lumen wall may create more stable contact
regions between the tubular elements and the lumen wall.
[0070] FIG. 14 illustrates an exemplary portion of a distal
delivery region. Distal delivery region 14 is a variation of that
of FIG. 12, wherein the spiral element comprises two spring
elements 18 arranged on either side of shuttle valve 50
incorporating a plurality of fluid controls 16.
[0071] FIGS. 15 and 16 illustrate perspective and end views,
respectively, of an alternative embodiment of the distal delivery
region. Distal delivery region 14 includes a tubular element with a
general spiral treatment configuration, and includes a plurality of
penetrating remodeling elements 19. Remodeling elements 19 can be
used to remodel tissue in a number of different ways. Procedurally,
the distal delivery region is delivered to a target lumen with
penetrating remodeling elements 19 retracted with the distal
delivery region in a delivery configuration. The elongate element
is then reconfigured into a spiral configuration. Remodeling
elements 19, which were retracted during delivery, are then
advanced distally through the elongate element into the
configuration as shown in FIGS. 15 and 16. The remodeling elements
may then be used to remodel the target tissue by any of mechanical
damage resulting from high velocity jet interactions such as
cutting or swelling and/or physical interaction of a cutting or
macerating element, delivering a tissue disruption agent
therethrough, delivering RF energy, or any combination thereof.
Penetrating remodeling elements 19 may comprise fluid controls as
described below.
[0072] FIGS. 17 and 18 illustrate two variations on the distal
delivery region shown in FIGS. 3-6. In both designs, the distal
delivery region control element 37 (which has a guide wire lumen
therethrough) is retracted proximally relative to outer sheath 36,
which foreshortens the distal delivery region 14. This in turn
causes tubular elements 31 to expand and engage the lumen wall. In
FIG. 17, each flexible tube incorporates needle valves including
apertures 52, as described herein. When tubular elements 31 are
expanded, fluid apertures 52 are moved into contact with the lumen
wall. In FIG. 17 a section of the outer sheath 36 has been removed
to show valve control wires 64 extending through the fluid supply
lines 65. The device of FIG. 18 expands in the same fashion, but
comprises shuttle valves (described in more detail herein) rather
than needle valves.
[0073] The exemplary alternative distal delivery region shown in
FIG. 18 is shown incorporating four shuttle valves, each comprised
of valve movable member 57 (see FIGS. 21 and 23), a valve
stationary member 58 (see FIGS. 21 and 23), and a plurality of
apertures 60. An alternate way to expand a distal delivery region
is to incorporate a balloon. FIGS. 19 and 20 show two exemplary
distal delivery regions incorporating shuttle valves. Both
embodiments comprise a balloon which is contoured to allow blood
flow when the balloon is inflated. Blood flow is maintained in a
spiral fluid path adjacent to the lumen contact zone comprising the
shuttle valve. In FIG. 19 fluid control 60 is a shuttle valve
incorporated within the balloon 24 and in FIG. 20 fluid control 60
is a shuttle valve incorporated on the balloon. These embodiments
may alternatively comprise traditional non perfusion balloons.
[0074] In some situations the delivery devices described herein may
be configured such that a single fluid control actuates a plurality
of apertures 60.
[0075] FIGS. 21-24 illustrate two variations on shuttle valves
capable of being incorporated in a distal delivery region. The
valve of FIGS. 21 and 22 (FIG. 22 is a close-up view of a portion
of the device in FIG. 21) incorporates one or more apertures 52 on
outer member 56 of the valve, and an inner member 55, axially
moveable with respect to outer member 56, incorporating a masking
aperture 53. Apertures 52 are smaller than masking aperture 53. An
individual aperture 52 is selectively addressed when the sliding
inner masking aperture 53 is slid into a position adjacent aperture
52. In one configuration, members 55 and 56 are sealed at their
distal ends 57 and 58 respectively. Alternatively, the member
adapted to be moved with respect to the other member may be left
open when the design is such that the length of tubing distal to
masking aperture 53 is long enough to cover all of apertures 52
distal to the addressed aperture. Inner member 55 and outer member
56 are configured such that the outer diameter of the inner member
and the inner diameter of the outer member are closely matched
thereby creating an annular region of minimum cross section and
high fluid resistance. Alternatively, or in addition to, the inner
movable member or sections thereof may be designed such that under
the loads experienced while pressurized it expands and thereby
decreases the annular cross section thereby further increasing the
fluid resistance.
[0076] In FIG. 21, by moving larger aperture 53 with respect to
smaller apertures 52 such that aperture 53 is in alignment with a
given smaller aperture, that smaller apertures 52 can be
selectively addressable, increasing the amount of fluid that flows
from that valve. When a given valve is addressed, the other valves
are not addressed. In this embodiment the valves may be selectively
addressable in series. That is, as aperture 53 is moved from a
first aperture 52 to a second aperture 52, the first and second
apertures are selectively addressed in series. Alternatively, when
movable member 53 is allowed a rotational degree of freedom around
the axis defined by its central lumen, the movable member 53 may be
rotated 90 degrees and moved past smaller apertures 52 without
addressing them, then rotated 90 degrees in the reverse direction
when aligned with the aperture intended to be addressed.
[0077] FIGS. 23 and 24 depict an alternative variation on a shuttle
valve wherein masking aperture 53 is located on outer stationary
member 56 and aperture 52 is located on inner movable member 55.
Masking aperture 53 can be used to an additional advantage as a
mask that creates a field of view 54 addressable by inner aperture
52. The aperture 52 may be rotated about the cylindrical axis of
the outer stationary member 56 within the mask forming a field of
view 54. The field of view 54 forms the core of the remodeled
volume of damaged tissue peripheral to the lumen. The field of view
54 may alternatively describe a slice in the tissue resulting from
the jet interaction with the tissue. By rotating aperture 52 out of
the field of view of masking apertures not intended to be
addressed, any selection of fields of view 54 defined by masks 53
may be addressed for fluid delivery.
[0078] In some embodiments, the fields of views illustrated in
FIGS. 23 and 24, and in other embodiments herein, illustrate
exemplary patterns in which tissue is cut or severed by the tissue
remodeling therapies described herein.
[0079] The apertures 52 described herein can fall within a range of
diameters, or surface areas when not circular in cross section. For
delivery flows in the range of about 1 to about 20 mL/min,
diameters of about 0.005 in to about 0.0005 in will be of
particular value. The aperture should be sized such that the peak
velocity of the outflow reaches a minimum of about 10 m/sec, with
about 75 to about 150 m/sec being more optimal for greater
penetration and minimizing erosion. In some situations velocities
of greater than about 150 m/sec will be useful in achieving even
greater penetration.
[0080] The tissue interface means described herein provide for a
means of stabilizing the fluid apertures in contact with tissue in
a manner that minimizes movement of the aperture relative to the
adjacent tissue. The risk of dissections associated with the use of
fluid jets is thereby minimized. Additionally, by incorporating of
distal fluid controls, the period over which agents are delivered
can be controlled. By providing jets of agent in short bursts of 1
second or less, preferably 100 msec or less, unexpected movements
will result in multiple punctate wounds as opposed to a linear
dissection.
[0081] Given the relatively small cross sectional areas associated
with the fluid apertures in the devices described herein, it is
generally advisable to filter liquid agents prior to use and/or to
incorporate filters proximal to the distal fluid controls.
[0082] FIG. 25 illustrates the spiraled distal delivery region from
FIG. 12 incorporated with a shuttle valve design from FIG. 23, and
expanded in renal artery 40. The pattern of tissue damage is
indicated by fields of view 54. FIG. 26 illustrates a view normal
to the direction of blood flow demonstrating how the projection of
such patterns normal to the axis of the lumen can produce both
dense and overlapping coverage further from the lumen and spaced
non-overlapping coverage closer to the lumen. The density of
jetting structures and associated fields of view may be increased
to a point where the remodeled zones themselves overlap. The
associated density and field of view required will be dependent on
the particular way in which the damage is created. Given an
aperture of relatively small dimension, as illustrated in the
smaller apertures described herein, the ratio of the volume of
damaged tissue close to the aperture, seeded by the field of view
54, can be minimized relative to volume of damage further away. As
illustrated, where the lumen is that of a renal artery, this means
minimizing damage to endothelium, tunica intima 46, the tunica
media, and tunica adventitia 47, with extensive damage to
adventitia 48. When desired, the aperture's field of view 54 may be
increased to correspondingly increase the damage at the tunica
media 47. As indicated above any of the fields of view indicated
may be addressed in any sequence by appropriately controlling the
movable member of shuttle valve 23. In this way more or less of the
renal nerve may be disrupted.
[0083] The devices of FIGS. 21 and 23 may be configured such that
only a single fluid control may be addressed at one time or such
that multiple fluid controls may be addressed at one time.
[0084] FIGS. 27-32 illustrate various configurations and aspects of
exemplary needle valves that can be activated from the proximal end
of the delivery system, allow for minimal leakage in a closed
configuration or high fluid resistance when not activated, allow
minimal fluid resistance in an open configuration, provide the
ability to provide a metered dose from the valve, and are capable
of both serial or parallel activation. All valves are activated by
a valve control member 64, which is adapted to be axially moved
(forward and back) within fluid supply section 65, both of which
terminate in a handle (not shown). In some instances there is also
a metering or delivery section 66. In FIGS. 27-29, the needle valve
is supplied by a pressurized fluid source maintained at relatively
constant pressure which is in fluid communication with the aperture
52 via supply section 65, within which is valve control element 64.
In any cross section within which valve control member 64 is
contained within the fluid supply section, there is a relatively
non-restrictive fluid flow cross section, shown in FIG. 27 as
annular region 63. Distal to the fluid supply section is delivery
valve section 66, which in the embodiment of FIGS. 27-29 is of
smaller diameter than the supply section. In association with the
valve section is needle element 61 which is disposed within
delivery section 66. The clearance between the needle and delivery
section lumen is small, such that it forms a narrow restrictive
annular region of relatively high fluid resistance 62 as compared
to that of the lumen with the needle removed. Additionally, the
fluid flow cross section of supply section 62 is much smaller than
63. For instance, for a particular concentration of ETOH and water,
a restrictive fluid flow cross section created by a 0.5 inch long
0.004 inch inner diameter needle in a 0.005 inch inner diameter
tube will have a fluid resistance of 450 psi/mL/min. The
corresponding resistance for the same tube without the needle will
be approximately 5 psi/mL/min. In comparison, a supply section
created by a 32 inch long tube with a 0.015 inch outer diameter and
a 0.010 inch outer diameter control wire will have a corresponding
fluid resistance of approximately 1 psi/mL/min. In this example the
fluid resistance of the system in the open configuration is
approximately 75 times less than that of the closed system, and in
a constant pressure environment would leak at a rate of about 1/75
the open rate in the closed configuration. In the configurations
represented in FIGS. 27 and 28, an aperture 52 is created on the
side of delivery section 66 near the sealed distal end. In the
configuration represented in FIG. 29, the aperture is the open
distal end of the delivery section.
[0085] A variation on the example of FIGS. 27-29 is represented in
FIGS. 30-32. FIG. 30 shows a needle valve in an open configuration
where the end of the needle is maintained just within the lumen of
the delivery section 66. In FIG. 31, the valve is partially closed
with a section of a restrictive fluid flow cross section 62
indicated. FIG. 32 shows the valve fully closed with the distal
face of the guide 69 seated against the proximal face of the end
seal of the supply section 65. If required, further increases in
fluid resistance can be attained in the fully closed position by
incorporating an elastomeric guide 69 or an elastomeric distal face
to guide 69 which would seal against the proximal face of the end
seal on the supply section 65. Guide 69 additionally incorporates
relieved areas to create a large fluid flow cross section 63.
[0086] FIGS. 33-35 illustrate an exemplary embodiment of a metering
valve configuration. Guide 69 is configured such that it forms a
narrow restrictive annular aperture with the end of the delivery
section 66, which in this configuration may be the end of the
supply section 65. When the valve control member 64 is actuated
proximally, fluid leaks across the restrictive fluid flow cross
section 62, filling the distal metered volume 67. At this point the
fluid resistance between the supply side and the delivery side is
the sum of that associated with the exit aperture 52 and the
restrictive cross section 62. When the valve control member 64 is
released the resistance associated with fluid flow across cross
section 62 goes to zero and the guide moves as a plug of delivery
fluid. The movement of the guide imparts minimal additional fluid
resistance to the system, thereby allowing the pressure across
aperture 52 to attain levels comparable to those seen with no guide
in place. This state remains in effect until the guide runs into
the distal sealed end 68 of the delivery section 66, as shown in
FIG. 35. At this point the outflow resistance becomes that
associated with the restrictive fluid flow cross section 62 and
aperture 52 again. In this way, the delivered volume--that volume
delivered under high pressure and at high velocity which penetrates
the intima--is that which was disposed distal to the guide plug
prior to its release. The delivered volume can therefore be
regulated and controlled, and can be adjustable. If required, the
rate at which the guide is withdrawn during the fill cycle can be
matched to that of the expected fluid flow across restrictive fluid
flow cross section 62 such that there is minimal negative pressure
generated across the guide 69. This configuration behaves
differently than other control elements in that the fluid
resistance across the control element remains constant but the
position of the control element is allowed to change. As
illustrated the travel of the guide 69 is defined by the amount of
proximal displacement of the guide from the distal end seal 68
which acts as its stop. In an alternate embodiment, not shown, the
displacement of the guide 69 may be controlled by alternate
mechanisms and the guides displacement may terminate proximal to
the end seal 68.
[0087] FIGS. 36 and 37 illustrate the distal delivery region of
FIGS. 15 and 16 deployed within a section of renal artery 40. In
FIG. 36 the end of elongate delivery member 13 just distal to
distal delivery region 14 can be seen centered in the vessel.
Penetrating remodeling elements 19 have been deployed from their
non-deployed configuration within the distal delivery region to
their deployed state, penetrating through intimal 46 and medial
layer 47 of the vessel and terminating in the adventitial layer 48.
Volumes of remodeled tissue 45 spiral through the adventitia, with
one intersecting nerve 43. FIG. 37 depicts a view normal to the
axis of blood flow for the vessel in which can be seen that the
primary volume of remodeled tissue occurs beyond the intimal and
adventitial layers.
[0088] In yet another embodiment as depicted in FIG. 38, a
penetrating remodeling element 19 is a needle. The needle has a
helical configuration and delivered while contained with an outer
sheath of a delivery section 13 of a delivery system, not shown. In
this configuration, the outer sheath of the delivery section has a
stiffness sufficient to maintain the spring element in a
straightened configuration. On delivery the remodeling element is
pushed distally out of the distal end of the outer sheath of the
delivery system until the distal end of the remodeling element has
passed into the vessel wall. The remodeling element is then
twisted, which in combination with the pre-set spiral configuration
allows the remodeling element 16 to screw its way around the vessel
within the adventitial layer. The remodeling element can be
comprised of a number of different configurations. In many of these
configurations it is a conductor that may be powered with RF to
deliver energy sufficient to ablate the surrounding tissue.
Alternatively, it may be powered in such a way as to electroporate
the surrounding tissue. The remodeling element may additionally be
porous such that an ablating agent (described herein) may be
delivered through the porous structure. It may alternatively be
coated with an ablative agent. In those embodiments where it is
used to deliver an ablative agent on or through its walls and it is
conductive the electroporative capability may be used to enhance
the action of the ablative compound delivered. When the remodeling
element is comprised of a needle, it may also be used to leave an
ablative element in the tract of its path as the element is removed
by a procedure in reverse of that by which it was delivered. The
material left may alternatively be one designed to absorb energy
provided by an external source such as a gel containing a ferrite
as mentioned elsewhere in this application.
[0089] In any of the configurations relying on the delivery of a
fluid agent at high velocity, the pressure may be adjusted between
delivery cycles. In this manner the volume and spatial
characteristics of the remodeled tissue volume may be adjusted. Of
particular value in such a situation is the incorporation of a
contrast agent within the delivered media which will provide visual
feedback on the remodeled volume via the particular imaging means.
Such imaging means include but are not limited to CT, MRI, and
ultrasound.
[0090] FIG. 42 provides a figurative representation of a delivery
system incorporating a distal fluid control configured as a shuttle
valve, while a representation of its fluidic performance is
illustrated in FIG. 39. The system comprises a fluid and pressure
source 20, which feeds a delivery system 10, as generally described
above. The delivery system is comprised of elongate delivery member
13 comprising a fluid supply section feeding into distal delivery
region 14, which comprises a fluid control terminating in aperture
52 from which a jet of fluid 51 is ejected under appropriate
conditions of alignment. FIG. 40 is a figurative representation of
the delivery system in terms of its resistive fluidic
characteristics. The elements are the fluid resistance of the fluid
source 83 contained within elongate delivery member 13, the fluid
resistance of the fluid path within the tissue interface portion
84, and the fluid resistance of control port 80. Each of these
elements has an associated capacitance which is not shown in this
representation. The control port behaves as a variable resistance
which is the primary characteristic under control. FIGS. 40 and 41
illustrate various aspects of the resistive fluidic performance of
these components. FIG. 40 represents the resistance associated with
the fluid control port 80, as a function of the displacement "d" of
its control element position, and the resistances for the supply
section and tissue interface portions of the system 83 and 84
respectively, which are not directly controllable in this
configuration and are essentially fixed. Key positions for the jet
aperture 52 relative to the masking aperture 53 are indicated on
the displacement axis d as "0", "a", and "b". The point "0"
corresponds to the position where the proximal edge of the jet exit
aperture aligns with the proximal edge of the jet masking aperture.
The position "a" corresponds to the point at which the distal edge
of the jet aperture aligns with the distal edge of the masking
aperture, and b represents a point where the proximal edge of the
jet exit aperture is distal to the distal edge of the jet masking
aperture by some distance a-b. As seen in the illustration, the
fluid resistance versus displacement characteristics of the shuttle
valve fluid control 80 has two distinct performance features. A
constant resistance 82 is demonstrated initially which is equal to
that associated with the cross section of the jet exit aperture. A
second increasing resistance 81 is demonstrated when the jet
aperture passes out of the masking aperture. This resistance
increases as the distance d increases. FIG. 41 illustrates a
representation of the expected outflow rate 90 as a function d
given the resistance characteristics represented in FIG. 40 and a
constant pressure supply. Outflow rate 90 is comprised of a high
constant rate of outflow 91 for displacements "0" to "a" and a
decreasing rate of outflow 92 for displacements "a" to "b". The
regions represented by displacements "0" to "a" correspond to the
on state and the displacement "b" correspond to the off state. The
system resistance will be the sum of the component resistances. The
scales indicated should be understood as arbitrary and the
magnitude of the difference in flow and resistance in the off state
versus the on state may be a few times to multiple orders of
magnitude.
[0091] FIG. 43 shows the system of FIG. 39 wherein the shuttle
valve is replaced by a needle valve. This system demonstrates
fluidic behavior similarly to that described for the shuttle valve
variation. However certain differences associated with actuation
and fabrication are notable and delineated below. In a system
incorporating multiple individually and selectively addressable
fluid controls, the shuttle valve based system may be configured
such that control elements are comprised of two parts as is
illustrated in FIGS. 21-24 above. The needle valve and metered
valve variations by contrast require a separate control element and
associated controllable member for each valve separately
addressable. In the needle valve variation the variable resistance
associated with the control element 80 is shifted to the position
of the tissue interface 84, the resistance of the tissue interface
and the jet exit apertures in the most distal position. Such an
arrangement does not lend itself to a serial arrangement as the
multiple valves require a common source which is proximal to the
control element.
[0092] Given the small size of many of the critical features
associated with the above described fluid controls and the extreme
sensitivity of the performance of the fluid controls to the
dimensions of these features, the ability to serially and or
individually address each fluid control has particular value where
uniformity of delivery is required. For instance, an individual
device may be calibrated in such a fashion that the outflow
resistance for each outflow is known and used to adjust the either
or both the static source pressure or the on time such that each
outflow behaves similarly with reference to the fluid delivery
during an injection cycle. In addition, as noted above, the fluid
media delivered may contain a contrast agent and the operator can
use the visual information to change the source pressure to vary
depth of penetration, duration of injection to adjust volume
delivered, or provide multiple injection cycles at a given location
to adjust volume of targeted tissue. The delivery cycle may
additionally be spread out over time such that an initial volume is
injected at an initial time, then an additional volume is injected
at a later time where enough time is allowed such that information
on the rate of diffusion of the delivered fluid is gained and
additional volumes may then be delivered in a fashion wherein the a
concentration of ablatant sufficient to ablate is maintained in the
remodeled target volume for a sufficient time to remodel the
tissue.
[0093] FIG. 44 represents yet another alternative for effecting
tissue remodeling where a fluid, gas, or mechanical rod may be used
to eject a component capable of external excitation as described
herein or alternatively a component which upon ejection springs
into a shape different than its delivery shape and in so doing
damages tissue in its vicinity, thereby causing tissue remodeling.
In FIG. 44 spring elements 101 are shown after ejection from distal
delivery region 30 through the wall of renal artery 40. As shown,
multiple spring elements 101 have been ejected from two separate
positions of distal delivery region 30. Spring elements 101 may be
configured such that the tines are held together for a period of
time past the ejection cycle. For instance they may be held
together by a water soluble binder and injected in a gas, oil, or
alcohol carrier. In this fashion, on residing within the tissue for
a period of time the binder will be solubalized and the tines
released. The release of the tines may be used to cut or macerate
the tissue surrounding the tines.
[0094] It has been demonstrated in the literature that the volume
of tissue affected by a needleless injection will be dependent on
the spatial velocity and temporal velocity profiles of the
injectate at the time of delivery. In particular, delivering a
volume of fluid into a tissue mass at high initial velocity
minimizes tissue damage at the entry point while allowing fluid to
penetrate deep into the tissue. Maintaining the outflow at a lower
velocity after the initial penetration facilitates an increase in
volume delivered through the initial wound. In the above described
fluid delivery systems, the control mechanism has been incorporated
at the distal region of the delivery system. This allows the
delivery system to be maintained at delivery pressures and thereby
minimizes the filtering effects of the long narrow delivery lumens
and system capacitance on the velocity profile of ejected fluid at
the exit aperture.
[0095] In another alternative embodiment of a tissue remodeling
device cutting or macerating devices may be delivered through or in
the manner that needles 16 in FIGS. 36 and 37 are delivered. Such
devices may be configured as slicing hooks or simple blades which
cut on being pushed as represented in FIG. 45. Additionally such
devices may be spun as an atherectomy blade to facilitate the
requisite remodeling as depicted in FIG. 46 through which the
rotatable cutting device of FIG. 45 is delivered. FIG. 47 shows a
device as in FIG. 36. While preferred embodiments of the present
disclosure have been shown and described herein, it will be obvious
to those skilled in the art that such embodiments are provided by
way of example only. Numerous variations, changes, and
substitutions will now occur to those skilled in the art without
departing from the disclosure. It should be understood that various
alternatives to the embodiments of the disclosure described herein
may be employed in practicing the disclosure.
* * * * *