U.S. patent application number 14/412387 was filed with the patent office on 2015-08-20 for methods, devices, and systems for postconditioning with clot removal.
The applicant listed for this patent is COGNITION MEDICAL CORP.. Invention is credited to Jonah Bernstein, Alexis Turjman.
Application Number | 20150230820 14/412387 |
Document ID | / |
Family ID | 49882624 |
Filed Date | 2015-08-20 |
United States Patent
Application |
20150230820 |
Kind Code |
A1 |
Turjman; Alexis ; et
al. |
August 20, 2015 |
METHODS, DEVICES, AND SYSTEMS FOR POSTCONDITIONING WITH CLOT
REMOVAL
Abstract
New devices, systems, and methods are disclosed for preventing,
treating, and/or at least minimizing ischemia and/or reperfusion
injury by restoring and/or modulating blood flow, particularly in
the cerebral vasculature where blood vessels are narrow and
tortuous. These devices, systems, and methods make it possible for
a clinician to adequately and systematically restore blood flow to
ischemic tissue while simultaneously modulating the blood flow to
minimize reperfusion injury.
Inventors: |
Turjman; Alexis; (Cambridge,
MA) ; Bernstein; Jonah; (Cambridge, MA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
COGNITION MEDICAL CORP. |
Cambridge |
MA |
US |
|
|
Family ID: |
49882624 |
Appl. No.: |
14/412387 |
Filed: |
July 5, 2013 |
PCT Filed: |
July 5, 2013 |
PCT NO: |
PCT/US2013/049428 |
371 Date: |
December 31, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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13844728 |
Mar 15, 2013 |
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14412387 |
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61668408 |
Jul 5, 2012 |
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Current U.S.
Class: |
606/159 |
Current CPC
Class: |
A61B 17/12036 20130101;
A61F 2/95 20130101; A61F 2/962 20130101; A61F 2/966 20130101; A61M
25/10 20130101; A61B 17/12031 20130101; A61B 17/12136 20130101;
A61B 17/12172 20130101; A61B 17/12109 20130101; A61B 17/3207
20130101; A61F 2/86 20130101; A61M 25/0082 20130101; A61B
2017/22067 20130101; A61F 2/844 20130101; A61B 17/320725 20130101;
A61B 2017/22065 20130101; A61B 2017/2215 20130101; A61B 2017/320716
20130101; A61F 2/82 20130101; A61M 2025/1095 20130101; A61B 17/221
20130101 |
International
Class: |
A61B 17/3207 20060101
A61B017/3207; A61M 25/10 20060101 A61M025/10 |
Claims
1. An assembly configured to treat ischemia in a patient,
comprising: a catheter with a proximal region, a distal region, and
a single lumen; a flow modulation member attached to the catheter
and comprising an inflatable balloon configured to reversibly
decrease and increase the flow of fluid through the blood vessel at
least twice, and thereby modulate blood flow through the blood
vessel, the flow modulation member comprises an inflatable balloon
configured to receive a balloon inflation aperture continuous with
the lumen; a pushwire with a proximal end and a distal end, wherein
the pushwire is at least partially within the single lumen; a flow
restoration member for increasing the flow of blood through the
region of the clot, coupled to the distal end of the pushwire; and
one or more sealing members attached to one of the pushwire and
catheter adapted to decrease the flow rate of inflating fluid
leaving the single lumen and inflate the balloon.
2. The assembly of claim 1, wherein the one or more sealing members
comprise a protrusion with an outwardly facing surface attached to
the pushwire at a location on the pushwire proximal to the flow
restoration member.
3. The assembly of claim 2, wherein the protrusion further slows
the flow of fluid through the lumen when the protrusion engages an
inwardly facing surface toward the pushwire at the distal region of
the catheter.
4. The assembly of claim 1, wherein the catheter lumen comprises a
first section in the proximal region and a second section in the
distal region, the first section of the lumen having a first area
in a plane normal to the catheter's central axis that is larger
than a second area in the plane normal to the catheter's central
axis in the second section of the lumen.
5. The assembly of claim 1, wherein one of the one or more sealing
members is electrically controlled, whereby an electric current
applied to the pushwire causes the sealing member to expand so as
to provide more resistance to the flow of fluid through the
catheter, whereby the flow modulation member is capable of
expanding to produce a desired seal in the blood vessel.
6. The assembly of claim 1, wherein the assembly is adapted to
operate with a pressure of the fluid less than 5 atm.
7. The assembly of claim 1, wherein a pump configured to perform
postconditioning cycles is connected to the lumen leading to the
inflatable balloon to deliver inflating fluid.
8. The assembly of claim 6, wherein the pump is configured to
provide at least two cycles of inflation and deflation and wherein
at least one of the cycles following the first cycle occurs without
additional operator intervention.
9. The assembly of claim 1, wherein the flow restoration member for
increasing the flow of blood through a blood vessel beyond a clot
comprises a self-expanding scaffold, adapted to engage a clot in a
blood vessel.
10. The assembly of claim 1, wherein the one or more sealing
members comprise a sealing tip at the distal end of the catheter,
wherein a luminal edge of the sealing tip comes in close proximity
with a sealing surface of the pushwire and slows the flow of fluid
through the lumen when the sealing surface of the pushwire is
placed through the sealing tip.
11. The assembly of claim 9, wherein the sealing tip allows the
flow restoration member to pass the sealing tip when the catheter
is translated relative to the pushwire.
12. An apparatus comprising: a catheter; a balloon disposed on the
catheter at a distal end of the catheter, the catheter defining a
lumen and including an orifice for inflating the balloon; a clot
capturing reperfusion member located near a distal end of the wire,
the wire being partially within the lumen of the catheter; and a
sealing interface between the wire and the lumen, nearer to the
distal end of the catheter than is the orifice for inflating the
balloon and adapted to seal the lumen so that the balloon may be
inflated.
13. The apparatus of claim 12, wherein the sealing interface
includes an outwardly facing surface of the wire and surface of the
lumen facing the pushwire.
14. The apparatus of claim 13, wherein the inwardly facing sealing
surface of the lumen has a smaller diameter than other portions of
the lumen of the catheter.
15. The apparatus of claim 13, wherein the outwardly facing surface
of the wire has a larger diameter than other portions of the
wire.
16-56. (canceled)
57. An assembly able to treat ischemia in the neurovasculature of a
patient, comprising: a catheter with a proximal end, a distal end,
and at least two catheter lumina; one or more flow modulation
members coupled to the catheter and comprising an inflatable
balloon configured to reversibly decrease and increase a flow of
fluid through a blood vessel at least twice, wherein the inflatable
balloon has a balloon lumen continuous with a first catheter lumen
and configured to receive inflating fluid from the first catheter
lumen, wherein a distal end of the first catheter lumen is closed;
one or more pushwires each with a proximal end and a distal end,
wherein a first pushwire of the one or more pushwires is placed at
least partially within a second catheter lumen; and one or more
flow restoration members are coupled to the first pushwire near a
distal end of the first pushwire.
58. The assembly of claim 57, wherein a flow restoration member of
the one or more flow restoration members comprises a self-expanding
scaffold configured to engage a clot in a blood vessel.
59. The method of claim 57, wherein a pump configured to perform
postconditioning cycles is connected to the lumen leading to the
inflatable balloon to deliver inflating fluid.
60. The method of claim 59, wherein the pump is configured to
provide at least two cycles of inflation and deflation and wherein
at least one cycle after the first cycle occurs without additional
operator intervention.
61-113. (canceled)
Description
RELATED APPLICATIONS
[0001] This application claims priority to and incorporates by
reference the entire contents of U.S. Provisional Application No.
61/668,408, filed on Jul. 5, 2012 and U.S. patent application Ser.
No. 13/844,728 filed on Mar. 15, 2013.
TECHNICAL FIELD
[0002] The present disclosure relates generally to methods,
devices, and systems for treating vascular disorders. More
specifically, the present disclosure relates to methods, devices,
and systems for restoring blood flow by, e.g., removing blood
clots, and/or modulating post-reperfusion blood flow.
BACKGROUND OF THE INVENTION
[0003] Ischemia, the restriction of blood supply to tissue, may
result in tissue damage in a process known as ischemic cascade.
Damage includes, but is not limited to, shortage of metabolic
requirements (i.e., oxygen and glucose), build-up of metabolic
waste products, inability to maintain cell membranes, mitochondrial
damage, and eventual leakage of autolysing proteolytic enzymes into
the cell and surrounding tissues. Brain ischemia may be chronic,
e.g., leading to vascular dementia, or acute, e.g., causing a
stroke. A stroke is the rapid decline of brain function due to a
disturbance in the supply of blood to the brain caused by a clot or
hemorrhage in a blood vessel. A clot may contain a thrombus,
embolus, and/or thromboembolus. An ischemic stroke is a stroke in
which a blood vessel is restricted or occluded by a clot.
[0004] Ischemic stroke is the fourth leading cause of death in the
United States, affecting over 795,000 patients per year and costing
tens of billions of healthcare dollars. See, e.g., Veronique L.
Roger et al., "Heart Disease and Stroke Statistics--2012 Update: A
Report from the American Heart Association." 125 Circulation
e2-e220 (2012). Furthermore, patients who survive an ischemic
stroke often require rehabilitation and management of symptoms
including loss of brain function, motor skills, and memory. The
extent of infarction (i.e., destruction of brain tissue) correlates
with the extent of these lingering effects of the stroke and the
mortality rate.
[0005] Of the existing treatment options for ischemic stroke, an
older method, but still the primary method used in the United
States, is to treat the clot with a clot-dissolving enzyme known as
tissue plasminogen activator ("tPA"). The use of tPA has two
primary drawbacks. First, tPA has limited effectiveness, in both
dissolving clots and providing overall benefits for the patients.
Many patients do not qualify for tPA treatment because they do not
arrive at the hospital within the effective time window of
approximately 4.5 hours after the onset of stroke. Even when used
within that window, tPA achieves only a limited decrease in the
overall mortality rate. Second, tPA may present adverse effects,
such as serious internal bleeding. See, e.g., Gotz Thomalla et al.,
"Two Tales: Hemorrhagic Transformation But Not Parenchymal
Hemorrhage After Thrombolysis Is Related to Severity and Duration
of Ischemia: MRI Study of Acute Stroke Patients Treated with
Intravenous Tissue Plasminogen Activator Within 6 Hours," 38(2)
Stroke 313-18 (2007).
[0006] A newer method to treat ischemic stroke is mechanical
thrombectomy, in which a device physically engages with a clot and
is used to drag the clot out of the body. Usually, an operator.
e.g., a surgeon, first establishes a path for the thrombectomy
device to reach a clot in the cerebral vasculature by inserting an
initial guidewire (or guiding catheter) into an artery in a lower
region of the body, such as the femoral artery. Then, the operator
steers the guidewire through the arteries leading up to the brain
and just past (i.e., distal to) the position of the clot. Favoring
whichever path poses least resistance, the guidewire passes either
between the clot and the blood vessel wall or through the clot. The
operator inserts a microcatheter over the initial guidewire to
follow its path until reaching a position distal to the clot. The
initial guidewire may be removed and replaced with a new guidewire
(hereinafter "pushwire" to differentiate from an initial
guidewire). This pushwire has a thrombectomy device attached to its
distal end to engage with the clot.
[0007] Currently, the most successful class of thrombectomy devices
is based on neurovascular stent technology. Like stents, which are
self-expandable and generally cylindrical, these devices tend to
expand to the shape of the blood vessel walls. Thrombectomy devices
may comprise thin metal struts arranged to create a cell pattern.
During device expansion, a clot may become enmeshed in the cells
and compressed against a blood vessel wall. At this point, blood
flow may be partially or fully restored in the vessel, thus
relieving ischemia.
[0008] Unfortunately, abrupt restoration of blood supply to
ischemic tissues may cause reperfusion injury, which is additional
damage to cerebral tissue, above and beyond damage caused by the
ischemia itself. For example, reperfusion results in a sudden
increase in tissue oxygenation, causing a greater production of
free radicals and reactive oxygen species that damage cells. The
restored blood flow also brings more calcium ions to the tissues
causing calcium overloading that may result in potentially fatal
cardiac arrhythmias and accelerated cellular self-destruction.
Furthermore, reperfusion may exaggerate the inflammation response
of damaged tissue, triggering white blood cells to destroy
otherwise viable damaged cells.
[0009] Reperfusion injury is highly significant and can visibly
increase the infarct size (i.e., destroyed tissue) by as much as
30%. See. e.g., Andrew Tsang et al., "Myocardial Postconditioning:
Reperfusion Injury Revisited," 289(1) Am. J. Physiol. Heart &
Circ. Physiol. H2-7 (2005); Heng Zhao et al., "Interrupting
Reperfusion as a Stroke Therapy: Ischemic Postconditioning Reduces
Infarct Size After Focal Ischemia in Rats," 26(9) J. Cereb. Blood
Flow & Metab. 1114-21 (2006); Giuseppe Pignataro et al., "In
Vivo and In Vitro Characterization of a Novel Neuroprotective
Strategy for Stroke: Ischemic Postconditioning," 28(2) J Cereb.
Blood Flow & Metab. 232-41 (2008).
[0010] Existing thrombectomy devices and/or systems do not
systematically or even adequately control the restoration of blood
flow so as to minimize and/or prevent reperfusion injury. Thus far,
the prevention of reperfusion injury has been limited to the field
of interventional cardiology. During the management of an ischemic
event in the heart, a cardiologist will treat the occlusion of a
vessel with stents and/or balloon angioplasty to restore blood
flow. Following reperfusion, a cardiologist may use an inflatable
balloon to block and unblock blood flow through the vessel in
intervals, thus modulating the resumed blood flow and minimizing
reperfusion injury in a process called postconditioning.
[0011] Existing postconditioning devices and/or systems (e.g.,
catheters with high longitudinal rigidity and large diameters) are
designed for the large arteries of the heart; however, the narrow
and tortuous arteries of the cerebral vasculature render these
existing devices and/or systems inadequate or at least less
desirable in the context of ischemic stroke.
[0012] Existing postconditioning devices and/or systems also fail
to incorporate simultaneous clot capture. In order to initiate
reperfusion and perform postconditioning simultaneously, both a
reperfusion member and flow modulation member must be disposed
concurrently in the same region. Particularly in the brain, where
space constraints make it difficult to fit both a reperfusion
member and a flow modulation member, no existing postconditioning
devices and/or systems are designed to simultaneously deploy a
reperfusion member, such as a clot-capturing reperfusion member,
and perform postconditioning for the ischemic tissue.
[0013] Thus, there remains a need for postconditioning devices,
systems, and methods designed to prevent, minimize, and/or treat
ischemic stroke and/or reperfusion injury by restoring and
modulating blood flow in the cerebral vasculature.
[0014] Meanwhile, in addition to overlooking reperfusion injury,
existing thrombectomy devices and/or systems are not designed to
consistently bind with, capture, and/or retrieve clots. In fact,
only about 30% of clots are successfully retrieved on a first pass
(i.e., a deployment of the thrombectomy device). After five passes,
10% of clots still remain lodged. Furthermore, in 10% of cases,
reperfusion is not even achieved while a thrombectomy device and/or
system is engaged with the clot. Thus, there also remains a need
for thrombectomy devices and/or systems that not only increase
binding with clots but also increase reperfusion by creating a
greater gap within the clot or between the clot and the blood
vessel wall.
SUMMARY OF THE INVENTION
[0015] The devices, systems, and methods of the present invention
are based on the recognition of the anatomic and physiologic
principles, particularly in the cerebral vasculature, underlying
reperfusion injury and ischemic stroke. The prior thrombectomy
and/or postconditioning art fail to recognize the importance of,
and provide methods and systems for, adequately controlling the
restoration of blood flow so as to minimize and/or prevent
reperfusion injury. The prior art also fails to sufficiently
address the arterial space constraints in the brain that limit the
positioning of devices and/or systems.
[0016] As described more fully in this specification, embodiments
of the present invention include methods for preventing, treating,
and/or at least minimizing ischemic stroke and/or reperfusion
injury by restoring and/or modulating blood flow, particularly in
the cerebral vasculature. The methods, generally referred to as
postconditioning, are performed with devices and systems, which are
adapted for use in the performance of the controlled restoration
and/or modulating blood flow. The devices, systems, and methods
described herein make it possible for a clinician to adequately and
systematically restore blood flow to ischemic tissue while
simultaneously modulating the blood flow to minimize reperfusion
injury. Some embodiments of the present invention specifically
enable postconditioning in the challenging dimensional constraints
of the brain. Some embodiments further enable improved binding with
clots and reperfusion by creating an increase within the
cross-sectional area between the clot and the blood vessel wall or
in the clot itself, particularly for clots that are resistant to
the weak engagement of existing thrombectomy devices and/or
systems.
[0017] The present invention addresses an unmet clinical need to
control reperfusion and prevent ischemia. Embodiments of the
present invention include systems and methods for preventing,
treating, and/or at least minimizing ischemic stroke and/or
reperfusion injury by restoring and/or modulating blood flow,
particularly in the cerebral vasculature. The systems and methods
of the present invention make it possible for a clinician to
systematically restore blood flow to ischemic tissue while
simultaneously modulating the blood flow to minimize reperfusion
injury. Some embodiments of the present invention specifically
enable postconditioning in the challenging dimensional constraints
of the brain (i.e. narrow and tortuous arteries of the cerebral
vasculature).
[0018] Some embodiments further enable improved binding with clots
and reperfusion by creating an increase in cross-sectional area
between the clot and the blood vessel wall or within the clot
itself, particularly for clots that are resistant to the weak
engagement of existing thrombectomy devices and/or systems. The
embodiments of the present invention include two features, a
reperfusion member and a flow modulation member. In an embodiment,
the flow modulation member may be coupled to a proximal region of
the catheter and include an inflatable balloon able to reversibly
decrease and increase the flow of fluid through the blood vessel at
least twice, and so modulate blood flow through the blood vessel.
According to other embodiments, the flow modulation member can take
an umbrella-like shape. In other embodiments various
pharmacological agents can be delivered to the treatment site to
reduce the size or effect of the ischemia.
[0019] These embodiments of the present invention are primarily
directed, therefore, to initiating reperfusion and performing
postconditioning simultaneously in a blood vessel with improved
devices, systems, and methods. These embodiments are designed to
prevent, minimize, and/or treat ischemia and/or reperfusion injury
by restoring and modulating blood flow in the cerebral vasculature,
as well as vasculature in the lungs, heart, pelvis, legs, and any
other part of a cardiovascular system in a living being (or in
vitro models thereof).
[0020] The embodiments of the invention include, described in
proximal to distal order, an expandable flow modulation device
located at the exterior of the catheter, a seal located at the
interior of the catheter, and a stent attached to a wire that can
protrude from the distal portion of the catheter. The expandable
membrane can manifest itself in a variety of formats, including,
but not limited to, an expandable membrane ("balloon") and a
collapsible diaphragm ("umbrella"). The seal format includes, but
is not limited to, spherical, conical, ovoid, and cylindrical, with
optional tapering at one or both ends of the device. The stent used
to capture the clot has formats including, but not limited to, a
mesh spherical surface, a mesh ovoid surface, and a mesh
cylindrical surface, which opens upon protrusion from the catheter.
The stent remains in place during the clot-capture process, as the
catheter depth is adjusted to simultaneously regulate reperfusion
with the aforementioned expandable flow modulation device at the
exterior of the catheter. Expansion and contraction of the exterior
can be conducted by methods including, but not limited to,
translation of components to effect expansion, pneumatics which can
drive gas to expand the flow modulation device, hydraulics which
can drive liquid to expand the flow modulation device, and
electromagnetic mechanisms.
[0021] In one embodiment, a method includes introducing a device
into a cerebral blood vessel that is at least partially blocked by
a clot, applying pressure to an internal wall of the cerebral blood
vessel to enhance blood flow in the vessel, postconditioning to
reduce reperfusion injury, removing at least part of the clot from
the vessel, removing the device from the cerebral blood vessel, the
application of pressure, the removal of the clot, and the
postconditioning occurring after the device is introduced and
before the device is removed from the vessel.
[0022] In an embodiment, the method step of postconditioning
includes at least partially occluding the vessel. In an embodiment,
the method steps of applying, removing, and postconditioning
comprise a single medical procedure. In an embodiment, the method
step of postconditioning further includes selectively permitting
flow through the vessel and reducing flow through the vessel in
prescribed sequence.
[0023] In one embodiment, an apparatus includes a catheter, an
expandable membrane ("balloon") disposed on the catheter at a
distal end of the catheter, the catheter including an orifice for
inflating the balloon, a stent in the vicinity of a distal end of a
wire that extends through a lumen to an end of the catheter, and a
sealing interface between the wire and the lumen, nearer to the
distal end of the catheter than is the orifice for inflating the
balloon, that is adapted to seal the lumen so that the balloon may
be inflated.
[0024] In an embodiment, the sealing interface of the apparatus
includes an outwardly facing surface on the wire and an inwardly
facing surface on the lumen. In an embodiment, the inwardly facing
sealing surface of the lumen has a smaller diameter than the other
portions of the lumen of the catheter. In an embodiment, the
outwardly facing surface of the wire has a larger diameter than
other portions of the wire.
[0025] In one embodiment, a device capable of transporting fluid
and a pushwire bearing a flow restoration member includes a
catheter with a lumen that has an inner surface, a pushwire,
including a sealing ring disposed toward the distal end of the
pushwire, wherein the sealing ring is sized to sealingly engage the
inner surface of the catheter so that when engaged the sealing ring
substantially blocks flow of the fluid through the catheter so that
inflating fluid may be directed into the balloon so as to cause
inflation of the balloon.
[0026] In an embodiment, the device is capable of transporting
fluid that contains one or more of the following: contrast agent,
tPA, cyclosporine, calpain inhibitors, sodium-calcium Na+/Ca2+
exchange inhibitors, monoclonal antibodies, temperature reducing
agents, agents that slow cell metabolism, plasminogen activator,
agents that may aid in removing a clot agents that aid in
dissolving, dislodging, or macerating clots, pharmaceuticals or
compounds commonly used for treating clots, preventing restenosis,
agents that prevent/reduce or accelerate healing of reperfusion
injury, intravascular device coatings such as vasodilators,
nimodipine, sirolimus, paclitaxel, anti-platelet compounds and
agents that promote the entanglement or attachment of a clot with a
reperfusion member such as fibronectin.
[0027] In one embodiment, an assembly configured to treat ischemia
in a patient includes a catheter with a proximal region, a distal
region, and a single lumen, a flow modulation member coupled to the
proximal region of the catheter and including an inflatable balloon
able to reversibly decrease and increase the flow of fluid through
the blood vessel at least twice, and thereby modulate blood flow
through the blood vessel, wherein the inflatable balloon has a
balloon inflation aperture continuous with the single lumen and
able to receive inflating fluid from the single lumen, a pushwire
with a proximal end and a distal end, wherein the pushwire is at
least partially within the single lumen, a flow restoration member
for increasing the flow of blood through the clot, coupled to the
distal end of the pushwire, and one or more sealing members adapted
to decrease the flow rate of inflating fluid leaving the single
lumen.
[0028] In an embodiment, one of the one or more sealing members of
the assembly is made of an electroactive compound, whereby applying
and/or altering an electric current applied to the pushwire causes
the electroactive sealing member to expand so as to provide more
resistance to the flow of fluid through the catheter, wherein the
flow modulation member is capable of expanding to produce a desired
seal. In an embodiment, the assembly further is adapted to operate
with a pressure of the fluid less than 5 atm. In an embodiment, the
flow restoration member for increasing the flow of blood through a
blood vessel beyond a clot includes a self-expanding scaffold,
adapted to engage a clot in a blood vessel.
[0029] In one embodiment, an aspect of the invention is a method
comprising the steps of introducing a device into a cerebral blood
vessel that is at least partially blocked by a clot and applying
pressure to an internal wall of the cerebral blood vessel to
enhance blood flow in the vessel. Postconditioning is then applied
to reduce reperfusion injury. Then, in one embodiment, the method
involves removing at least part of the clot from the vessel and
then removing the device from the cerebral blood vessel. Each of
the steps in this embodiment, the application of pressure, the
removal of the clot, and the postconditioning occurs after the
device is introduced and before the device is removed from the
vessel. In this method, the step of postconditioning may comprise
at least partially occluding the vessel. Another aspect of this
method includes performing the steps of applying, removing, and
postconditioning comprise a single medical procedure. In another
aspect of the method the step of postconditioning may include
selectively permitting flow through the vessel and reducing flow
through the vessel in prescribed sequence.
[0030] Another aspect of the invention is an apparatus that
includes a catheter, a balloon disposed on the catheter at a distal
end of the catheter. The catheter according to the embodiment
includes an orifice for inflating the balloon. A stent is provided
in the vicinity of a distal end of a wire that extends through a
lumen to an end of the catheter. In another aspect of this
embodiment, a sealing interface is disposed between the wire and
the lumen, nearer to the distal end of the catheter than is the
orifice for inflating the balloon that is adapted to seal the lumen
so that the balloon may be inflated. The sealing interface in this
embodiment may include an outwardly facing surface on the wire and
an inwardly facing surface on the lumen. Additionally, the inwardly
facing sealing surface of the lumen has a smaller diameter than the
other portions of the lumen of the catheter. In another aspect of
this embodiment, the outwardly facing surface of the wire has a
larger diameter than other portions of the wire.
[0031] A further embodiment of the invention includes a device
capable of transporting fluid and a pushwire bearing a flow
restoration member. In this embodiment, the device includes a
catheter, which includes a lumen that has an inner surface, a
pushwire that includes a sealing ring disposed toward the distal
end of the pushwire. The sealing ring is sized to sealingly engage
the inner surface of the catheter so that when engaged the sealing
ring substantially blocks flow of the fluid through the
catheter.
[0032] In another embodiment, an assembly configured to treat
ischemia in a patient includes a catheter with a proximal region, a
distal region, and a single lumen and a flow modulation member
coupled to the proximal region of the catheter and including an
inflatable balloon able to reversibly decrease and increase the
flow of fluid through the blood vessel at least twice, and so
modulate blood flow through the blood vessel. The inflatable
balloon according to another embodiment has a balloon inflation
aperture continuous with the single lumen and able to receive
inflating fluid from the single lumen, a pushwire with a proximal
end and a distal end, wherein the pushwire is at least partially
within the single lumen, a member for increasing the flow of blood
through the clot, coupled to the distal end of the pushwire; and
one or more sealing members adapted to decrease the flow rate of
inflating fluid leaving the single lumen.
[0033] The catheter in the above embodiment may comprise various
devices, which can be used to seal the catheter, which can, when
desired, inflate a balloon for a reperfusion. A first section in
the proximal region and a second section in the distal region, the
area in the second section of the lumen, in the plane normal to the
central axis of the catheter, being smaller than the area in the
first section of the lumen, in the plane normal to the central axis
of the catheter. A sealing member may comprise a protrusion with an
outwardly facing surface attached to the pushwire at a location on
the pushwire proximal to the flow restoration member. The
protrusion slows the flow of fluid through the lumen when the
protrusion engages an inwardly facing surface at the distal region
of the catheter.
[0034] In another embodiment, a sealing member may comprise a
sealing tip at the distal end of the catheter. A luminal edge of
the sealing tip is designed to come in close proximity with a
sealing surface of the pushwire and slows the flow of fluid through
the lumen when the sealing surface pushwire is placed through the
sealing tip. In this embodiment, the sealing tip allows the flow
restoration member to pass the sealing tip when the catheter is
translated relative to the pushwire.
[0035] Another aspect of the inventive method disclosed in this
application includes a method of using an assembly able to treat
ischemia in a patient, the steps of the method include first,
identifying a blood clot in a blood vessel: second, inserting a
catheter into the blood vessel, the catheter including a proximal
region, a distal region, and a single lumen, wherein a pushwire
with a proximal end and a distal end is placed at least partially
within the single lumen; third, modulating blood flow in the blood
vessel by selectively decreasing and increasing the flow of fluid
through the blood vessel with a flow modulation member at least
twice. The flow modulation member is coupled to the distal region
of the catheter and includes an inflatable balloon having a balloon
inflation aperture with the single lumen and adapted to receive
inflating fluid from the single lumen, wherein one or more sealing
members are provided along the lumen to reduce the volumetric flow
rate of inflating fluid leaving the single lumen; and fourth,
increasing the flow rate in the blood vessel by translating the
catheter relative to the pushwire to deploy a flow restoration
member, wherein the flow restoration member is coupled to the
pushwire near the distal end of the pushwire and comprises a
self-expanding scaffold able to engage the clot.
[0036] An aspect of this method includes the feature that the
catheter used in the method comprises a first section in the
proximal region and a second section in the distal region, the area
in the second section of the lumen, in the plane normal to the
central axis of the catheter, being smaller than the area in the
first section of the lumen, in the plane normal to the central axis
of the catheter. Additionally, another aspect of the invention
includes the feature that one or more a sealing ring may be coupled
to the pushwire at a location in the single lumen proximal to the
flow restoration member, wherein the sealing ring is able to engage
the distal region of the catheter. Additionally and alternatively,
the one or more a sealing tip may be coupled to the distal end of
the catheter, and the sealing tip is adapted to selectively
sealingly engage when the catheter is translated relative to the
pushwire. In addition, according to this embodiment, the sealing
tip is able to allow the flow restoration member to pass the
sealing tip when the catheter is translated relative to the
pushwire.
[0037] Another embodiment of the invention includes an assembly
able to treat ischemia in a patient with an intermediate catheter
with a proximal region, a distal region, and a single intermediate
lumen. A flow modulation member is coupled to the distal region of
the intermediate catheter and comprises an inflatable balloon to
reversibly decrease and increase the flow of fluid through a blood
vessel for modulating blood flow through the blood vessel. The
inflatable balloon has a balloon lumen continuous with the single
intermediate lumen and receives inflating fluid from the lumen of
the intermediate catheter. Also included in this assembly is a
microcatheter with a single microcatheter lumen and the
microcatheter is at least partially within the lumen of the
intermediate catheter. A pushwire having a proximal end and a
distal end is adapted to be at least partially within the lumen of
the microcatheter. Also included in the assembly of this embodiment
is a flow restoration member coupled to the distal end of the
pushwire and comprising a self-expanding scaffold able to engage a
clot in a blood vessel and one or more sealing members able to
reduce the volumetric flow rate of inflating fluid leaving the
single intermediate lumen.
[0038] In some embodiments of this invention, the self-expanding
scaffold is a stent. Further, in some embodiments, the intermediate
catheter includes a first section in the proximal region and a
second section in the distal region, the area in the second section
of the lumen, in the plane normal to the central axis of the
catheter, being smaller than the area in the first section of the
lumen, in the plane normal to the central axis of the intermediate
catheter. One or more sealing members may be included that have a
protrusion which reduces the space between the pushwire and the
protrusion through which fluid can flow around the location of the
protrusion coupled to the microcatheter, so that the protrusion may
facilitate the inflation of the balloon when the protrusion is
within or near the distal region of the intermediate catheter. In
some embodiments the protrusion is annular. Additionally or
alternatively, a sealing tip may be coupled to the distal end of
the intermediate catheter, wherein a luminal edge of the sealing
tip comes in close proximity with the pushwire and slows the flow
of fluid through the lumen when the pushwire is placed through the
sealing tip.
[0039] Another aspect of the method of this invention may include a
method of using an assembly able to treat ischemia in a patient.
The steps of this method may include, identifying a target blood
clot in a blood vessel; inserting into the blood vessel an
intermediate catheter with a proximal region, a distal region, and
a single intermediate catheter lumen, wherein a microcatheter with
a single microcatheter lumen is at least partially within the
single intermediate catheter lumen, wherein a pushwire with a
proximal end and a distal end is at least partially within the
lumen of the microcatheter; modulating blood flow in the blood
vessel by reversibly decreasing and increasing the flow of fluid
through the blood vessel with a flow modulation member at least
twice, wherein the flow modulation member is coupled to the distal
region of the intermediate catheter and comprises an inflatable
balloon having a balloon lumen continuous with the single
intermediate lumen and able to receive inflating fluid from the
single intermediate lumen; reducing the rate of inflating fluid
leaving the single intermediate lumen by translating the
intermediate catheter relative to the microcatheter so that the
protrusion slows the flow of fluid through the lumen when the
protrusion engages the distal region of the intermediate catheter;
and increasing the flow rate in the blood vessel by translating the
catheter relative to the pushwire to deploy a flow restoration
member.
[0040] In another aspect of the invention the flow restoration
member used in the method may be coupled to the pushwire near the
distal end of the pushwire and includes a structure or material for
addressing a clot, such as macerating, transforming or dissolving
the clot. The structure or material will engage the clot by either
direct physical contact, direct/indirect energy contact or by
distribution of pharmacological agent. In one embodiment the
structure could be a scaffold, which may be self-expanding and
capable of addressing the clot by direct physical contact. In still
another aspect of the invention, the catheter used in the method
may include a first section in the proximal region and a second
section in the distal region, the area in the second section of the
lumen, in the plane normal to the central axis of the catheter,
being smaller than the area in the first section of the lumen, in
the plane normal to the central axis of the catheter. The method
may employ one or more sealing members used in the method comprise
a protrusion coupled to the pushwire at a location in the single
lumen proximal to the flow restoration member. The protrusion slows
the flow of fluid through the lumen when the protrusion engages the
distal region of the catheter. Additionally or alternatively a
sealing tip may be coupled to the distal end of the catheter,
wherein the sealing tip is able to engage the pushwire when the
catheter is translated relative to the pushwire. Additionally, the
luminal edge of the sealing tip comes in close proximity with the
pushwire and slows the flow of fluid through the lumen when the
pushwire is placed through the sealing tip.
[0041] In still another embodiment of the invention an assembly
able to treat ischemia in a patient is described. In this
embodiment, the invention includes a catheter with a proximal end,
a distal end, and at least two catheter lumina; one or more flow
modulation members coupled to the catheter and comprising an
inflatable balloon able to reversibly decrease and increase the
flow of fluid through the blood vessel with a flow modulation
member at least twice, wherein the inflatable balloon has a balloon
lumen continuous with a first catheter lumen and able to receive
inflating fluid from the first catheter lumen, wherein the distal
end of the first catheter lumen is closed; one or more pushwires
with a proximal end and a distal end, wherein the pushwire is
placed at least partially within a second catheter lumen; and one
or more flow restoration members coupled to the pushwire near the
distal end of the pushwire. In this embodiment, a flow restoration
member may include a self-expanding scaffold able to engage a clot
in a blood vessel.
[0042] In another method of the invention, the assembly is able to
treat ischemia in a patient. In this embodiment the use of the
assembly includes the following steps: identifying a blood clot in
a blood vessel; inserting a catheter into the blood vessel the
catheter including a proximal end, a distal end, and at least two
catheter lumina, wherein a pushwire with a proximal end and a
distal end is placed at least partially within a first catheter
lumen; modulating blood flow in the blood vessel by reversibly
decreasing and increasing the flow of fluid through the blood
vessel with a flow modulation member at least twice, wherein the
flow modulation member is coupled to the proximal region of the
catheter and comprises an inflatable balloon having a balloon lumen
continuous with a second catheter lumen receiving inflating fluid
from the second catheter lumen, wherein one or more sealing members
slow the flow rate of the inflating fluid that leaves the second
catheter lumen; and increasing the flow rate in the blood vessel by
translating the catheter relative to the pushwire to deploy a flow
restoration member. In this method, the flow restoration member is
coupled to the pushwire near the distal end of the pushwire and
comprises a self-expanding scaffold able to engage the clot.
[0043] In still a further embodiment of the invention an assembly
able to treat ischemia in a patient includes: an intermediate
catheter with a proximal end, a distal end, and at least two
intermediate catheter lumina; one or more flow modulation members
coupled to the intermediate catheter and comprising an inflatable
balloon or membrane able to reversibly reduce and increase the flow
of fluid through the blood vessel at least twice for modulating
blood flow through the blood vessel, wherein the inflatable balloon
has a connecting lumen continuous with a first intermediate
catheter lumen and receives inflating fluid from the first
intermediate catheter lumen, wherein the distal end of the first
intermediate catheter lumen is closed; one or more microcatheters
with a microcatheter lumen, wherein the microcatheter is at least
partially within a second intermediate catheter lumen; one or more
pushwires with a proximal end and a distal end, wherein the
pushwire is at least partially within the microcatheter lumen; and
one or more flow restoration members coupled to near the distal end
of the pushwire and comprising a self-expanding scaffold that
engages a clot in a blood vessel.
[0044] In another embodiment of the method according to the
invention an assembly is used to treat ischemia in a patient. The
steps of the method include: identifying a blood clot in a blood
vessel; inserting into the blood vessel an intermediate catheter
with a proximal end, a distal end, and at least two intermediate
catheter lumina, wherein a microcatheter with a microcatheter lumen
is placed at least partially in a first intermediate catheter
lumen, wherein a pushwire with a proximal end and a distal end is
placed at least partially in the microcatheter lumen; modulating
blood flow in the blood vessel by reversibly decreasing and
increasing the flow of fluid through the blood vessel with a flow
modulation member at least twice, wherein the flow modulation
member is coupled to the distal region of the intermediate catheter
and comprises an inflatable balloon having a balloon lumen
continuous with a second intermediate catheter lumen and able to
receive inflating fluid from the second intermediate catheter
lumen: and increasing the flow of blood in the blood vessel by
translating the catheter relative to the pushwire to deploy a flow
restoration member, wherein the flow restoration member is coupled
to pushwire near the distal end of the pushwire and comprises a
self-expanding scaffold able to engage the clot.
[0045] The present invention in one embodiment is an assembly
adapted to engage a clot in a blood vessel. The assembly includes a
catheter with a proximal end, a distal end, and at least one lumen;
a pushwire with a proximal end and a distal end, wherein the
pushwire is at least partially within the at least one lumen; and a
reperfusion member coupled to the pushwire near the distal end of
the pushwire and comprising a self-expanding scaffold that is
capable of engaging a clot in a blood vessel when the catheter is
moved so that the expanding scaffold is not completely within the
catheter. The scaffold includes open cells formed by a pattern of
struts and the cells have a hexagonal cell shape able to facilitate
engagement with the clot.
[0046] The present invention in another embodiment is an assembly
adapted for engaging a clot in a blood vessel. The assembly
includes a catheter with a proximal end, a distal end, and at least
one lumen; one or more pushwires with a proximal end and a distal
end, wherein the pushwire is at least partially within the at least
one lumen; and a reperfusion member coupled to the distal end of
the pushwire and comprising a self-expanding scaffold to engage a
clot in a blood vessel when the catheter is retracted so as to at
least partially not surround the expanding scaffold, wherein the
scaffold comprises open cells formed by a pattern of struts,
wherein at least one of the struts has a cross-sectional shape with
an angle less than 180 degrees oriented such that the angle
protrudes outward from the scaffold to facilitate engagement with
the clot.
[0047] According to another method of the present invention a clot
in a blood vessel can be engaged. The method includes the steps of:
identifying a blood clot in a blood vessel; inserting into the
blood vessel a catheter with at least one lumen, wherein a pushwire
with a proximal end and a distal end is placed at least partially
within the at least one lumen, wherein a reperfusion member
comprising a self-expanding scaffold is coupled to the distal end
of the pushwire; aligning the distal end of the catheter within or
distal to the clot; retracting the catheter to unsheathe and allow
the scaffold to expand within the blood vessel, wherein the
scaffold comprises open cells formed by a pattern of struts,
wherein the cells have a hexagonal cell shape able to facilitate
engagement with the clot; and extracting any clot material engaged
by the scaffold by removing the catheter and the pushwire from the
blood vessel.
[0048] In still another embodiment of the invention, the
specification describes a method for engaging a clot in a blood
vessel. The steps include: identifying a blood clot in a blood
vessel; inserting into the blood vessel a catheter with at least
one lumen, wherein a pushwire with a proximal end and a distal end
is placed at least partially within the at least one lumen, wherein
a reperfusion member comprising a self-expanding scaffold is
coupled to the pushwire near the distal end of the pushwire;
placing the distal end of the catheter close to the distal end of
the clot; retracting the catheter to unsheathe and allow the
scaffold to expand within the blood vessel, wherein the scaffold
comprises open cells formed by a pattern of struts, wherein at
least one of the struts has a cross-sectional shape with an angle
less than 180 degrees oriented such that the angle protrudes
outward from the scaffold to facilitate engagement with the clot;
and extracting any clot material engaged by the scaffold by
removing the catheter and the pushwire from the blood vessel.
[0049] In another aspect of the invention assembly is disclosed
that is able to prevent and/or treat ischemic stroke in a patient.
The assembly according to this embodiment includes a flow
restoration member comprising a self-expanding scaffold capable of
engaging a clot in a cerebral blood vessel; and a flow modulation
member to reversibly decreasing and increasing the flow of fluid
through the blood vessel with the flow modulation member at least
twice, performing one or more postconditioning cycles in the
cerebral blood vessel, wherein the members are able to be used
simultaneously to prevent and/or treat ischemic stroke.
[0050] The invention in another embodiment includes a method of
preventing and/or treating ischemic stroke in a patient. In this
embodiment the steps of the method include: identifying a blood
clot in a cerebral blood vessel; inserting an assembly able to
prevent, mitigate and/or treat ischemic stroke into the blood
vessel, the assembly comprising: a flow restoration member
comprising a self-expanding scaffold able to engage a clot in a
cerebral blood vessel; and a flow modulation member able to
modulate blood flow in a cerebral blood vessel, wherein the members
are able to be used simultaneously to prevent, mitigate, reduce
and/or treat ischemic stroke: deploying the scaffold to restore
blood flow in the cerebral blood vessel; and performing one or more
postconditioning cycles with the flow modulation member by
reversibly decreasing and increasing the flow of fluid through the
blood vessel at least twice.
[0051] The present invention is according to another embodiment, a
device for modulating blood flow, the device includes: a flow
modulation member having a plurality of self-expanding struts and a
membrane capable of blocking blood flow; a pushwire, wherein the
flow modulation member is attached to the pushwire; and a
microcatheter with a lumen sized to receive at least a portion of
the pushwire, the membrane capable of blocking blood flow attached
to the microcatheter, wherein relative movement between the
pushwire and the microcatheter in one direction unsheathes the flow
modulation member, allowing the flow modulation member to expand,
and wherein relative movement between the pushwire and the
microcatheter in the opposite direction re-sheathes the flow
modulation member, causing the flow modulation member to
retract.
[0052] Another embodiment of the present invention is a device for
modulating blood flow, the device includes: a flow modulation
member comprising a microcatheter and an inflatable balloon
attached to the microcatheter adapted to selectively reduce blood
flow; a fluid conduit associated with the microcatheter for
conducting inflation fluid between a proximal side of the
microcatheter and the balloon, wherein the conduit is flexible and
contiguous with the microcatheter. In this embodiment, the conduit
may be a tube that travels outside the microcatheter. The conduit
according to this embodiment may be disposed in a helical
arrangement outside the microcatheter. The conduit of this
embodiment may be a hollow space between an inner wall and an outer
wall of the microcatheter, the inner and outer wall of the
microcatheter connected at selected locations along its length.
[0053] In another aspect of the invention, device for engaging with
a blood clot or embolus includes: a reperfusion member attached to
a push wire and having a plurality of self-expanding struts with an
angular cross-sectional profile, wherein a point of the profile
faces outward from the clot-capturing reperfusion member; and a
microcatheter for housing the clot-capturing reperfusion member,
wherein relative movement between the pushwire and the
microcatheter in one direction unsheathes the member, causing the
member to expand, and wherein relative movement between the
pushwire and the microcatheter in the opposite direction
re-sheathes the member, allowing the member to retract. In aspect,
the system for achieving and modulating reperfusion may include a
flow modulation member capable of blocking blood flow; a pushwire
with a self-expanding clot-capturing reperfusion member attached
toward the distal end, and, a pushwire, adapted to be introduced to
the vasculature through the microcatheter and wherein both the
clot-capturing reperfusion member is attached to the pushwire; and
the flow modulation member is also attached to the pushwire; and a
microcatheter adapted to receive at least a portion of the
pushwire, wherein relative motion between the guidewire and the
microcatheter in one direction is capable of unsheathing both the
flow modulation member and the clot-capturing reperfusion member,
causing one or both members to expand, and wherein relative motion
between the guidewire and the microcatheter in an opposite
direction is capable of re-sheathing one or both of the flow
modulation member and the clot-capturing reperfusion member,
causing one or both members to retract.
[0054] A system for achieving and modulating reperfusion of a
vessel in the cerebral vasculature following ischemic stroke is
another aspect of the invention. In this embodiment, the system
includes: a flow modulation member capable of reversibly reducing
blood flow; a mechanism for selectively causing blood flow of the
vessel to increase; and the flow modulation member adapted to reach
the location of the clot via the endovasculature; the system
adapted so that the flow modulation member is capable of performing
at least two iterations of reducing and then varying flow in the
vessel proximate the site of the clot.
[0055] A method for modulating blood flow is another aspect of the
invention. In this embodiment the method includes: inserting a
microcatheter into a blood vessel; inserting a pushwire into the
microcatheter, wherein a flow modulation member is attached to the
pushwire, wherein the member has a plurality of self-expanding
struts and a membrane capable of blocking blood flow; translating
the pushwire or the microcatheter relative to one another in one
direction to unsheathe the member, allowing the member to expand;
translating the pushwire or the microcatheter relative to one
another in an opposite direction to re-sheathe the member, causing
the member to retract; and repeating the translating steps at least
once to modulate blood flow.
[0056] An embodiment of the invention can also be described as
method for modulating blood flow for the treatment of ischemic
stroke. In this embodiment the method includes: inserting a
microcatheter and a fluid conduit into a blood vessel, wherein the
conduit is flexible and contiguous with the microcatheter, wherein
a flow modulation member is attached to the microcatheter, and
wherein the member has an inflatable balloon capable of blocking
blood flow; conducting inflation fluid to the balloon, causing the
balloon to expand; conducting inflation fluid from the balloon,
causing the balloon to retract; and repeating the conducting steps
at least once to modulate blood flow.
[0057] Another embodiment of the invention can be described as a
method for removing a blood clot or embolus, the method includes
the steps of: inserting a microcatheter into an occluded blood
vessel; inserting a pushwire into the microcatheter, wherein a
self-expanding reperfusion member is attached to the guidewire and
has a plurality of self-expanding struts with an angular
cross-sectional profile, wherein a point of the profile faces
outward from the member toward the clot or embolus; translating the
guidewire or the microcatheter relative to one another in one
direction to unsheathe the member, causing the member to expand to
engage the clot or embolus.
[0058] The invention presently disclosed in one embodiment is a
method for achieving and modulating reperfusion, the method
according to this embodiment includes the steps of: inserting a
microcatheter into an occluded blood vessel; inserting a pushwire
into the microcatheter, wherein both a flow modulation member
capable of blocking blood flow and a self-expanding reperfusion
member are attached to the pushwire; translating the pushwire or
the microcatheter relative to one another in one direction to
unsheathe one or both of the flow modulation member and the
reperfusion member, causing one or both members to expand; and
translating the guidewire or the microcatheter relative to one
another in an opposite direction to re-sheathe one or both of the
flow modulation member causing the flow modulation member to
retract; and repeating the translating steps at least once to treat
an occlusion and modulate reperfusion.
[0059] The present invention in another embodiment is a method for
achieving and modulating reperfusion, the method includes the steps
of: inserting a microcatheter into an occluded blood vessel;
inserting a pushwire into the microcatheter, wherein a
self-expanding reperfusion member is attached to the guidewire; and
a flow modulation member capable of blocking or reducing blood flow
is attached to the microcatheter; translating the pushwire or the
microcatheter relative to one another in one direction to unsheathe
the reperfusion member, causing the reperfusion member to expand;
and performing an expansion step to cause the flow modulation
member to occlude or lessen flow; and repeating the expansion at
least once to modulate reperfusion.
[0060] Finally, the present invention in an embodiment is a system
for achieving and modulating reperfusion, the system includes:
three catheters where in at least one region, a narrow catheter is
inside an intermediate catheter, and the intermediate catheter, is
inside a largest catheter; wherein a pusher member is at least
partially inside the narrow catheter; and the intermediate catheter
has a flow modulation member capable of reversibly occluding or
blocking flow near its distal end; a reperfusion member; a
pushwire, wherein the reperfusion member is attached to the
pushwire; wherein relative translation between the pushwire and the
smallest catheter in one direction is capable of unsheathing the
reperfusion member, causing the capture member to expand.
[0061] The details of one or more embodiments of the present
invention are set forth in the accompanying drawings and the
description below. Other features, objects, and advantages of the
present invention will be apparent from the description and
drawings, and from the claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0062] The invention and the following detailed description of
certain embodiments thereof may be understood with reference to the
following figures:
[0063] FIGS. 1A-1B illustrate endoluminal assemblies with a balloon
and sealing ring in accordance with some embodiments of the present
invention. In FIG. 1B the sealing ring is in a manner that allows
the balloon to be deflated;
[0064] FIG. 2 illustrates a pushwire with a tapered distal end in
an endoluminal assembly in accordance with some embodiments of the
present invention;
[0065] FIGS. 3A-3B are an isometric view and a detail view,
respectively, of a sealing ring system in accordance with some
embodiments of the present invention;
[0066] FIGS. 4A-4D and 5 illustrate methods of using a sealing ring
system with a single-lumen balloon catheter in accordance with some
embodiments of the present invention;
[0067] FIG. 6 illustrates a sealing ring with a conical shape and a
microcatheter with a matching distal tip in accordance with some
embodiments of the present invention;
[0068] FIGS. 7A-7B illustrate alternative catheter distal tip
designs for preventing a sealing ring from advancing beyond the
distal tip of a catheter in accordance with some embodiments of the
present invention;
[0069] FIG. 8A is a side view of an aperture in the catheter for
inflating a balloon according to some embodiments of the present
invention, and FIG. 8B is a sectional view taken along sectional
line 8B-8B of FIG. 8A;
[0070] FIG. 9 illustrates an alternative passage shape designed for
the flow of inflating fluid between the lumina of a catheter and an
inflatable flow modulation member in accordance with some
embodiments of the present invention;
[0071] FIGS. 10A-10B are process flow charts for performing
postconditioning in accordance with some embodiments of the present
invention:
[0072] FIGS. 11A-11B illustrate a sectional view of a catheter and
a detail section view, respectively, of a scaling member which is
constructed using an electro active polymer when the sealing member
is in an unexpanded state;
[0073] FIGS. 11C-11D illustrate a sectional view of a catheter and
a detail sectional view, respectively, of a catheter with a sealing
member constructed using an electro active polymer according to an
embodiment of the present invention when the sealing member is in
the expanded state:
[0074] FIGS. 12A-12B are process flow charts for performing
postconditioning in accordance with some embodiments of the present
invention.
[0075] FIG. 13 illustrates a cross sectional view with a sealing
ring system with an intermediate balloon catheter in accordance
with some embodiments of the present invention;
[0076] FIGS. 14A-14B are process flow charts for performing
postconditioning in accordance with some embodiments of the present
invention;
[0077] FIGS. 15A-15B illustrate cross-sectional views of an
alternative embodiment of the present invention using an electro
active polymer, which constricts around the inner microcatheter
according to the present invention in the constrained and open
configurations, respectively;
[0078] FIGS. 16A-16B are process flow charts for performing
postconditioning in accordance with some embodiments of the present
invention;
[0079] FIGS. 17-18 illustrate alternative sealing tip designs for
assemblies with a single-lumen balloon catheter in accordance with
some embodiments of the present invention;
[0080] FIGS. 19A-19B are process flow charts for performing
postconditioning in accordance with some embodiments of the present
invention;
[0081] FIGS. 20A-20B illustrate cross-sectional views of assemblies
with a double-lumen balloon microcatheter in accordance with some
embodiments of the present invention;
[0082] FIGS. 20C-20E illustrate cross-sectional views of various
microcatheters of varying numbers of lumina in accordance with some
embodiments of the present invention;
[0083] FIGS. 21A-21B illustrate a process flow chart for performing
postconditioning in accordance with some embodiments of the present
invention;
[0084] FIGS. 22A-22B illustrate perspective views of assemblies
with a double-lumen balloon catheter in accordance with some
embodiments of the present invention;
[0085] FIGS. 23A-23B are process flow charts for performing
postconditioning in accordance with some embodiments of the present
invention
[0086] FIGS. 24-25 illustrate alternative designs for a multiple
lumen balloon catheter in accordance with some embodiments of the
present invention;
[0087] FIGS. 26A-26B are process flow charts for performing
postconditioning in accordance with some embodiments of the present
invention
[0088] FIGS. 27A-27C illustrate different views of assemblies with
an umbrella-like flow modulation member in accordance with some
embodiments of the present invention;
[0089] FIG. 28 is a view parallel to the central longitudinal axis
of an umbrella-like flow modulation member supported by a lattice
strut structure in accordance with some embodiments of the present
invention;
[0090] FIG. 29 illustrates an embodiment of an umbrella-like flow
modulation member supported by six primary struts in accordance
with some embodiments of the present invention;
[0091] FIG. 30 is a view perpendicular to the central longitudinal
axis of an umbrella-like flow modulation member supported by six
primary struts in accordance with some embodiments of the present
invention;
[0092] FIGS. 31A-31D illustrate alternative strut curvatures of an
umbrella-like flow modulation member in accordance with some
embodiments of the present invention;
[0093] FIGS. 32A-32B illustrate the angle between the central
longitudinal axis and a primary strut axis in an umbrella-like flow
modulation member during working and resting states in accordance
with some embodiments of the present invention;
[0094] FIGS. 33A-33E illustrate various embodiments of primary
strut cross sections with different shapes and dimensions in
accordance with some embodiments of the present invention;
[0095] FIGS. 34A-34D illustrate various embodiments of flow
modulation members with different methods of attaching the struts
to a pushwire in accordance with some embodiments of the present
invention;
[0096] FIGS. 35-36 illustrate various embodiments of an
umbrella-like flow modulation member supported by primary and
secondary struts from a view perpendicular to the central
longitudinal axis in accordance with some embodiments of the
present invention;
[0097] FIG. 37 is a cross-sectional view perpendicular to the
central longitudinal axis of an umbrella-like flow modulation
member, with its primary struts covered by a membrane having a
reinforced distal edge, in accordance with some embodiments of the
present invention;
[0098] FIGS. 38A-38B illustrate an umbrella-like flow modulation
member having a secondary strut with a zigzag configuration around
the longitudinal axis in accordance with some embodiments of the
present invention;
[0099] FIG. 39 illustrates an umbrella-like flow modulation member
having primary struts encased within the membrane in accordance
with some embodiments of the present invention:
[0100] FIG. 40 illustrates an embodiment of an umbrella-like flow
modulation member, with its primary struts encased within a
membrane having a reinforced distal edge, from a cross-sectional
view perpendicular to the central longitudinal axis in accordance
with some embodiments of the present invention;
[0101] FIGS. 41A-41G illustrate various views of an embodiment of
an umbrella-like flow modulation member, with its primary struts
covered by the membrane, in accordance with some embodiments of the
present invention;
[0102] FIGS. 42A-42D and 43 illustrate an embodiment of an
umbrella-like flow modulation member, with its primary struts
encased within the membrane, from various angles in accordance with
some embodiments of the present invention;
[0103] FIG. 44 illustrates an embodiment of an umbrella-like flow
modulation member with its primary struts covered on the outer side
by the membrane in accordance with some embodiments of the present
invention;
[0104] FIGS. 45A-45C illustrate alternative designs for a flow
modulation member accordance with some embodiments of the present
invention;
[0105] FIGS. 46A-46C and 47A-47B illustrate various embodiments for
combining clot capture and flow modulation functionalities within
the same member in accordance with some embodiments of the present
invention;
[0106] FIG. 48A-48B are process flow charts for performing
postconditioning in accordance with some embodiments of the present
invention:
[0107] FIGS. 49A-49B are a cross-sectional view and a detail
sectional view, respectively, of an embodiment of a flow modulation
member in accordance with some embodiments of the present
invention;
[0108] FIGS. 50A-50B illustrate a process flow chart for performing
postconditioning in accordance with some embodiments of the present
invention;
[0109] FIGS. 51A-51C and 52 illustrate alternative designs of a
reperfusion member in accordance with some embodiments of the
present invention:
[0110] FIG. 53 illustrates a reperfusion member with radiopaque
material lengthwise in accordance with some embodiments of the
present invention:
[0111] FIG. 54 illustrates a reperfusion member with a hexagonal
cell structure in accordance with some embodiments of the present
invention;
[0112] FIGS. 55A-55D illustrate alternative cell shapes for a
reperfusion member in accordance with some embodiments of the
present invention:
[0113] FIGS. 56-57 are alternative two-dimensional cell patterns
for a reperfusion member, depicted as developed surfaces, in
accordance with some embodiments of the present invention;
[0114] FIG. 58 illustrates reperfusion member struts with increased
surface area in accordance with some embodiments of the present
invention;
[0115] FIGS. 59A-59K are cross-sectional views of alternative strut
designs for a reperfusion member in accordance with some
embodiments of the present invention;
[0116] FIGS. 60A-60B are three-dimensional views of reperfusion
member struts with a triangular cross-section in accordance with
some embodiments of the present invention;
[0117] FIG. 61A-61F illustrate steps for deploying a reperfusion
member and flow modulation member in accordance with some
embodiments of the present invention; and
[0118] FIGS. 62A-62J are postconditioning schedules to illustrates
various embodiments of alternative timed intervals of occlusion
i/reperfusion cycles for flow modulation in accordance with some
embodiments of the present invention.
DETAILED DESCRIPTION
[0119] Embodiments of the present invention include methods for
preventing, treating, and/or at least minimizing ischemic stroke
and/or reperfusion injury by restoring and/or modulating blood
flow, particularly in the cerebral vasculature. The methods,
generally referred to as postconditioning are performed with
devices and systems, which are adapted for use in the performance
of the controlled restoration and/or modulating of blood flow. The
devices, systems, and methods described herein make it possible for
a clinician to adequately and systematically restore blood flow to
ischemic tissue while simultaneously modulating the blood flow to
minimize reperfusion injury. Some embodiments of the present
invention specifically enable postconditioning in the challenging
dimensional constraints of the brain. Some embodiments further
enable improved binding with clots and reperfusion by creating an
increase within the cross-sectional area between the clot and the
blood vessel wall or in the clot itself, particularly for clots
that are resistant to the weak engagement of existing thrombectomy
devices and/or systems. Contributing features, such as flexibility
and radial force, will be discussed further herein.
[0120] As used herein, "proximal" indicates a direction closer to
the entry point of the catheter. "Distal" indicates a direction
further away from the entry point. Moreover, distal and proximal
refer to regions either on the device as a whole or on a specific
component and thus designate relative position rather than a fixed
point. The term cross-sectional "diameter" does not necessarily
imply a circular shape with respect to a cross-section of, for
example, a balloon with an elliptical cross-section Diameter can
also refer to the longest dimension of a cross-section of a
component of any shape, including, but not limited to ellipsoids,
ovoids, polygons and any path-connected volume.
[0121] A "seal" or an object adapted for blocking ("sealing") an
opening, such as a sealing ring or sealing tip for sealing a
catheter lumen, may completely or partially block fluid passage
from one or both sides of the seal. Additionally the seal may
increase resistance to flow or decrease the volumetric rate of
fluid passing through the opening. Likewise, an object adapted for
"occluding" flow in a passage may completely or partially block
flow or at least increase resistance to flow or decrease the
volumetric rate of a substance passing through the passage. A
clot-capturing reperfusion member is an apparatus that achieves at
least partial reperfusion of an occluded artery while attempting
capture or partial capture of the clot. A flow modulation member is
a device that is suitable to regulate and control the flow of
blood, after the occlusion has been partially or completely
resolved.
Reperfusion and/or Flow Modulation Devices and Systems
[0122] According to some embodiments of the present invention, a
flow modulation system may include an initial guidewire, a
microcatheter, an intermediate catheter, and/or a flow modulation
member. According to some embodiments of the present invention, a
reperfusion system may include an initial guidewire, a
microcatheter, an intermediate catheter, a pushwire and/or a
reperfusion member. In further embodiments of the present
invention, a flow modulation system and a reperfusion system may be
combined to systematically and effectively control the restoration
of blood flow so as to prevent, minimize, and/or treat ischemic
stroke and/or reperfusion injury by restoring and modulating blood
flow in a blood vessel, such as an cerebral artery.
[0123] FIGS. 1A-B, for example, illustrate endoluminal assemblies
in accordance with some embodiments of the present invention. The
assembly in FIG. 1A, which is disposed in a blood vessel with a
wall 114, includes an inflated flow modulation member 100, a
microcatheter 102, a pushwire 106, and a reperfusion member 108
that is attached to the pushwire with an attachment ring 110. The
pushwire 106 is an example of the variety of "wires" that may be
used to implement the embodiments of the present invention. These
devices are situated within the luminal wall 114 of a blood vessel
(only one wall is illustrated) with blood flowing from the proximal
direction 116 to the distal direction 118. FIGS. 1A-1B also
illustrate, to be described below in accordance with some
embodiments, a sealing ring 104, a narrowed portion b of a
microcatheter 120, wherein the space in the catheter lumen, between
the pushwire 106 and the luminal wall of the microcatheter 102
decreases 120 from proximal luminal space 126 to distal luminal
space 128, an inflation fluid passage 122, a radiopaque marker 124,
and an attachment region 130 to attached the flow modulation
member's membrane to the catheter. FIG. 1B shows the flow
modulation member deflated, in a configuration that is more
permissive to flow. FIG. 2 illustrates a pushwire 106 with a
tapered distal end leading to an endoluminal assembly 108 in
accordance with some embodiments of the present invention
[0124] According to some embodiments of the present invention, an
initial guidewire or access wire may be included and used to
navigate an initial path through the vasculature from a point of
insertion into the body (located, e.g., at the groin) to a location
in a blood vessel of a clot and/or ischemic region (e.g., a
cerebral artery). A guidewire may be advanced beyond the clot
and/or ischemic region to allow sufficient clearance for catheters
and devices to advance through the vessel in accordance with
embodiments of the present invention.
[0125] According to some embodiments of the present invention, a
guidewire may be manufactured from one or more materials including,
but not limited to, gold, nitinol, platinum, stainless steel,
nickel, titanium, and tungsten. In some embodiments, a guidewire
may be plated with radio-opaque materials, such as gold or
platinum, to aid visibility during a procedure. In further
embodiments, a guidewire may have some form of exterior coating to
reduce friction and/or provide other advantages. Exterior coatings
may include, but are not limited to, a silicone coating to reduce
friction, a hydrophilic coating to lubricate, an
anti-thrombogenic/Heparin coating to inhibit clotting, a
hydrophobic coating to provide greater tactile response, and a
polytetrafluoroethylene (PTFE) coating to reduce friction.
[0126] According to some embodiments of the present invention, one
or more catheters or flexible tubes may be inserted and used to
deliver devices and/or fluids to the clot and/or ischemic region.
According to some embodiments, a catheter may have one or more
lumina. A catheter may be advanced over the inserted guidewire,
which enables the catheter to follow its predefined pathway to the
point of treatment. According to some embodiments, "catheters" may
include, but is not limited to, a microcatheter, an intermediate
catheter, and a larger catheter (the "larger" designation refers to
the size of the catheter relative to the other catheters. While
portions of the specification may refer to a "large" catheter, the
references should be interpreted from the perspective of the other
catheters used in conjunction with the invention described
herein.
[0127] According to some embodiments of the present invention, a
microcatheter may be used to deliver devices and/or fluids to the
clot and/or ischemic region of the blood vessel. These devices and
fluids may include, but are not limited to, flow modulation
members, reperfusion members, inflating fluids, and medications
(e.g., tPA).
[0128] According to some embodiments of the present invention, an
intermediate catheter (e.g., size 5 French) may be used to
establish a conduit to a position closer to the clot and/or
ischemic region of the blood vessel, preserve a path to the clot,
and/or decrease the time needed for multiple passes. An
intermediate catheter may be used to deliver devices and/or fluids
including, but not limited to, microcatheters, flow modulation
members, reperfusion members, inflating fluids, and drugs (e.g.,
tPA). An intermediate catheter may also be used to contain or
aspirate clot material once a reperfusion member is pulled into the
catheter.
[0129] According to some embodiments of the present invention, a
large catheter (e.g., size 6 French, such as ENVOY.RTM. Guiding
Catheter available from DePuy Orthopedics, Inc. (Warsaw, Ind.)) may
be used to establish a conduit for the guidewire and catheters
through larger blood vessels, preserve that path, and decrease the
time needed for multiple passes. A larger catheter may also be used
to contain or aspirate clot material once a reperfusion member is
pulled into the catheter.
[0130] According to some embodiments of the present invention, a
catheter may be manufactured from materials including, but not
limited to, silicone rubber, nitinol, nylon, polyurethane,
polyethylene terephthalate (PETE) latex, and thermoplastic
elastomers. In further embodiments, catheters may have some form of
exterior or interior coating to reduce friction, lubricate, inhibit
clotting, provide greater tactile response, and/or provide other
advantages. Coatings may include, but are not limited to, a
silicone coating to reduce friction, a hydrophilic coating to
lubricate, an anti-thrombogenic/Heparin coating, a hydrophobic
coating, and a PTFE coating. The interior and/or exterior surface
of any of the catheters described in this invention may include a
material or treatment to reduce friction.
[0131] Following removal of an initial guidewire, a pushwire may be
inserted into a lumen of a microcatheter that has been placed over
the initial guidewire in accordance with embodiments of the present
invention. This "pushwire" carries one or more distal devices, such
as a flow modulation member and a reperfusion member. A pushwire
may be inserted and guided along a predefined pathway to the
location of a clot and/or ischemic region in the body to deliver
distal devices, generally by translation. According to some
embodiments, when a microcatheter is retracted, a distal device on
the pushwire may be unsheathed by translation of the microcatheter
in the proximal direction. In further embodiments, a distal device
on the pushwire may be resheathed by translation of the
microcatheter into an intermediate catheter. A pushwire may taper
toward the distal end to provide more latitudinal flexibility and
room for distal devices. FIG. 2 illustrates a guidewire 106 with
tapering in region 200 in accordance with some embodiments of the
present invention. In addition to the distally tapered pushwire
106, FIG. 2 illustrates a sealing ring 104 between the pushwire 106
and a microcatheter 102, and a clot capture member 108 that is
attached to the pushwire 106 with an attachment ring 110. In
preferred embodiments, the diameter of a pushwire is about 0.010
inches. However, pushwires with diameters ranging from
approximately 0.008 inches to 0.018 inches may be used.
[0132] According to some embodiments of the present invention, a
pushwire may be manufactured from one or more materials including,
but not limited to, gold, nitinol, platinum, stainless steel,
nickel, titanium, and tungsten. In some embodiments, a pushwire may
be plated with radio-opaque materials, such as gold or platinum, to
aid visibility during a procedure. In further embodiments, a
pushwire may have some form of exterior coating to reduce friction
and/or provide other advantages. Exterior coatings may include, but
are not limited to, a silicone coating to reduce friction, a
hydrophilic coating to lubricate, an anti-thrombogenic/Heparin
coating to inhibit clotting, a hydrophobic coating to provide
greater tactile response, and a PTFE coating to reduce
friction.
[0133] According to some embodiments, a delivery handle and winged
steering apparatus, which remain outside the body, may be used to
facilitate the insertion and/or control the movements of
guidewires, catheters, pushwires, and distal devices, by allowing
an operator to impart greater torque.
[0134] According to some embodiments of the present invention, a
reperfusion member is any mechanical device or chemical entity
adapted to achieve reperfusion. A clot-capturing reperfusion member
is a type of reperfusion device that engages with a clot in a blood
vessel, with the goal of removing the clot (preferably from the
body entirely) in accordance with some embodiments. In some
embodiments, a clot-capturing reperfusion member may be a distal
device, that is, the clot-capturing reperfusion member may be
coupled to the distal end of a pushwire and delivered to the
location of a clot via the lumen of a catheter. A pass is an
attempt to macerate, dislodge, and/or remove clot material.
According to some embodiments, a pass may consist of navigating a
guidewire past the location of a clot, translating a catheter over
the guidewire and past the clot, exchanging the guidewire for a
pushwire coupled with a reperfusion member, such as a
clot-capturing reperfusion member. If a first pass is not
successful, a new pass may require repeating one or more of these
steps. Reperfusion members generally and improved variations
thereupon are described in greater detail elsewhere herein in
accordance with some embodiments of the present invention.
Reperfusion members whose function is to restore flow in a blood
vessel are included in a larger group of flow restoration members.
Both reperfusion members and flow restoration members may have a
variety of configurations suitable for the purpose of the present
invention.
[0135] According to some embodiments of the present invention, a
flow modulation member is any device adapted to modulate blood flow
by, for example, reversibly occluding a blood vessel. A flow
modulation member may partially or completely occlude a blood
vessel, for example, in intervals, with the goal of
postconditioning an ischemic region, particularly to prevent and/or
minimize reperfusion injury, in accordance with some embodiments.
In some embodiments, a flow modulation member may be a distal
device, that is, the flow modulation member may be coupled to the
distal end of a pushwire and delivered to the location of a clot
via the lumen of a catheter. In other embodiments, a flow
modulation member may be an inflatable member that is coupled to
the distal end of a pushwire, a microcatheter, or an intermediate
catheter.
[0136] For embodiments in which a flow modulation member inflates
and deflates to reversibly occlude a blood vessel, a lumen of a
catheter may be used as a conduit for inflating fluid. In some of
these embodiments, a port may be added to the proximal end of the
catheter for pumping the inflating fluid. Other ports may be
provided for inserting other fluids and devices, such as a probe
for monitoring pressure in the inflatable member. Flow modulation
members generally and improved variations thereupon are described
in greater detail elsewhere herein in accordance with some
embodiments of the present invention.
[0137] According to some embodiments, a flow modulation member is
positioned proximal to a clot and/or reperfusion member in order to
reversibly control occlusion at the same time that a reperfusion
member is first engaged with a clot to begin reperfusion. A flow
modulation member should be positioned close to the clot and/or
reperfusion member to minimize the probability of interference with
from a collateral artery feeding the reperfused blood vessel
between the flow modulation member and the clot, but not so close
as to disturb the clot or reperfusion member. In preferred
embodiments, the proximity of a flow modulation member is selected
to maximize the extent to which a reperfused blood vessel receives
the benefits of postconditioning. For example, in the embodiments
shown in FIGS. 1A-1B, the flow modulation member 100 is designed
with a balloon of 2.4 mm diameter (at its target level of
inflation) for blood vessels with a diameter of 2 mm, and is
positioned so that the location the center of the balloon is 12 mm
proximal to the distal end of the microcatheter. The distance
between the center of the balloon and the distal end of the
microcatheter may range from 5 mm to 40 mm.
Single-Lumen Balloon Embodiments of a Flow Modulation Member
[0138] According to some embodiments of the present invention, the
flow modulation member consists of an expandable membrane
("balloon"), which may have some features similar to balloons used
for cardiac postconditioning and/or balloon catheters. However, one
critical difference between the present embodiments and balloons
used in other parts of the body is that this flow modulation
balloon and its inflating-fluid conduit must be able to navigate
the narrow, winding blood vessels of the brain. Existing inflatable
tube configurations (which may, for example, be inflated with
saline solution), particularly those that may be used in connection
with a clot treating system, are not capable of effectively
reaching the parts of blood vessels where clots tend to occur.
Thus, embodiments are designed to overcome the obstacles of size
and flexibility while maintaining the ability to inflate and
deflate rapidly, as controlled by an operator or programmable
device.
Single-Lumen Balloon Microcatheters with Pushwire-Bearing Sealing
Rings
[0139] FIGS. 1A-1B and 3A-3B illustrate unique assemblies, in
accordance with some embodiments of the present invention,
including a sealing ring 104 mounted on a pushwire 106 and a
balloon 100 mounted on a microcatheter 102 at attachment regions
130. The configurations provide enhanced navigability and allows
for the delivery of the reperfusion member 108 at the location of
the clot. Clots tend to lodge in the Middle Cerebral Artery, where
the vasculature is particularly tortuous. Current single-lumen
balloon microcatheters cannot be used to deliver stent-based
reperfusion members because their mode of action is incompatible
with stent delivery. Current single-lumen balloon microcatheters
have a seal at the distal end that exactly fits the diameter of the
appropriate guidewire. Therefore, the distal seal on current single
lumen balloon microcatheters would interfere with stent-based
reperfusion members attempting to exit the microcatheter's distal
end. Narrow catheters, of which microcatheters are an example, are
also suitable for implementing the embodiments of the present
invention.
[0140] The sealing ring 104 assembly, positioned at the distal end
of the pushwire 106, before the reperfusion member 108 (i.e., with
distance a between the sealing ring 104 and the attachment ring 110
for the reperfusion member 108), allows for a reperfusion member to
be compatible with a balloon microcatheter. The sealing ring 104
allows for a sealing at narrower region b with increased diameter,
so that the reperfusion member 108 has ample space to pass through
the sealing region without risking jamming the assembly. The ring
completes the seal upon entering the sealing region b. Therefore
the sealing ring 104 enables the narrow sealing region b to be
wider than the diameter of the pushwire.
[0141] The preferred length of the sealing ring is approximately 2
mm. However, different dimensions for the sealing ring may be used
(e.g., from approximately 1 mm to 5 mm in length). The diameter of
the sealing ring is preferred to be the same as the inner diameter
of the narrower region b of the microcatheter (toward the distal
end). It is anticipated that matching diameters will provide
adequate sealing while minimizing the risk of assembly jamming.
However, different dimensions for the sealing ring may be used
(e.g. from 0.010'' to 0.030'' in diameter).
[0142] The sealing ring can be attached to the pushwire in many
ways. The preferred method is swaging. Other methods that may be
used include, but are not limited to, interference fitting and
soldering. In the preferred embodiment, the sealing ring is
composed of the same material as that of the pushwire. This
material is preferred to be stainless steel, although other
materials, such as platinum-tungsten alloys, may be used.
[0143] There are numerous ways that a sealing ring on the pushwire
can be used to create a seal that will permit the reperfusion
member to pass through as well as facilitate postconditioning. The
embodiments above are only examples.
[0144] The preferred embodiment is a microcatheter with a
single-walled balloon operated in conjunction with a
pushwire-bearing a sealing ring. The cross-sectional profile of the
microcatheter narrows 120 at the distal end, such that when the
microcatheter is mounted on the pushwire, the sealing ring creates
a seal when the sealing ring is in the narrower region b of the
microcatheter.
[0145] A double lumen catheter, having a separate lumen for the
inflating fluid, would not need a seal around the surface of the
pushwire. The second lumen for the balloon-inflating fluid would be
within the walls of the microcatheter itself. Even without supports
(e.g. in a floating double lumen design), both tubes are advanced
simultaneously making the entire assembly more rigid.
[0146] The sealing ring allows for the saline solution, pushwire,
and reperfusion member to share a single lumen. In the embodiment
shown in FIGS. 1A, 1B, 3A, 3B there is space 126 between the
pushwire 106 and the luminal wall of the microcatheter 102 to allow
the inflating solution to travel through the lumen of the catheter
102, through inflation passages 122, and into the lumen of the flow
modulation member 100 to inflate the balloon. The space 126 is
identified in FIGS. 1A and 1B. Additionally, this space 126 ensures
reduced friction between the reperfusion member and the
microcatheter, during the translation of one with respect to the
other. The sealing ring 104 is positioned proximally to the
reperfusion member 108. The balloon microcatheter has a double
lumen, at the locus of the balloon 100 (the membrane of the balloon
being a lumen)--but a single-luminal wall everywhere else. The
inner lumen of the microcatheter 102 bears inflating holes 122 (two
holes in the embodiment shown) that connect the lumen of the
balloon to the inner layer, to let the inflating fluid reach the
cavity of the balloon. When translated into the narrower portion of
the microcatheter, the sealing ring creates a seal that prevents
the saline solution from flowing past the sealing ring 104 and
freely out of the distal end of the microcatheter. Once the sealing
ring 104 is advanced into the narrower portion b of the
microcatheter, pumping solution through the proximal end of the
microcatheter will result in the inflation of the balloon.
[0147] As noted previously, in some embodiments the sealing
mechanism is mounted on the pushwire and not protruding from the
inner wall of the catheter. If the sealing member were mounted on
the microcatheter, the reperfusion member would need to pass
through the seal and might become jammed in the process. In other
words in order to prevent the inflating solution from flowing out
the distal end of the microcatheter, the lumen of the microcatheter
would need to be flush with the pushwire, at some location distal
to the balloon. This seal around the pushwire would interfere with
the translation of the reperfusion member.
[0148] The sealing ring is preferred to be rounded on both the
proximal and distal ends to promote ease of entering the narrower
portion of the microcatheter as well as re-entering the
microcatheter. The sealing ring would only need to re-enter the
microcatheter if the microcatheter is retracted too far in the
proximal direction (e.g., beyond the proximal end of the sealing
ring) from the reperfusion member during the procedure. However, it
is suggested that the microcatheter cover the sealing ring at all
times. That is the operator should not pull the microcatheter
proximally to the extent that the distal 118 end of the
microcatheter is proximal to the sealing ring 104.
[0149] The diameter of the distal end of the microcatheter does not
widen in some embodiments (although in other embodiments this might
make it easier for the sealing ring to backer-enter the
microcatheter, should it fall out) because such a widening of the
distal end of the microcatheter would hamper navigability of the
microcatheter.
[0150] The preferred diameter shown of the pushwire is about
0.010''. However, pushwires with diameters ranging from about
0.008'' to about 0.018'' may be used.
Microcatheters Compatible with Pushwire-Bearing Sealing Rings
[0151] In the preferred embodiment, the inner diameter of the
microcatheter 102 (excluding the narrower region b at the tip) is
greater than the diameter of the sealing ring 104.
[0152] The inner diameter throughout the microcatheter may be the
same as the diameter of the sealing ring; however, this is not the
preferred embodiment.
[0153] Increasing the inner diameter of the microcatheter 102
slightly, in the preferred embodiment, will serve to prevent the
inflating fluid from being pushed forward by the sealing ring 104
(e.g., such as in a plunger-barrel assembly) because inflating
fluid will be able to travel freely around the sealing ring, at
times when the sealing ring is not within the sealing region.
Importantly for some embodiments, having the majority of the inner
diameter of the microcatheter 102 be greater than the diameter of
the sealing ring 104 can serve to reduce friction between the
microcatheter and the sealing ring. This friction could be
meaningful given that the sealing ring 104 would encounter it
throughout its journey through the microcatheter 102 and especially
given the tortuous curves that the assembly will take. The
microcatheter 102 will have this sufficient diameter from the
proximal end until near the distal end, where the diameter narrows
(shown at reference numeral 120) to the size of the sealing ring
104 so that a seal can be created.
[0154] In FIGS. 1A, 1B, 3A and 3B, the inner lumen of the
microcatheter 102 narrows at the tip. This creates a seal only when
the sealing ring 104 is within the narrowed portion b of the lumen.
The narrowed region b may be at the last few centimeters of the
tip, start from after the inflating holes 122, or in the last
centimeter from the distal end. A slightly longer narrowed region b
provides for greater position flexibility for the microcatheter 102
(relative to the clot) while being able to operate the balloon
100.
[0155] In a preferred embodiment the length of the sealing area
b--the portion of the microcatheter 102 that is narrower and
thereby creates a seal when the sealing ring 104 is inside--is less
than the length of the pushwire 106 between the distal end of the
sealing ring and the proximal end of the reperfusion member 108.
This allows for the reperfusion member to be fully released, while
permitting the operator the option to selectively have a seal or
not have a seal. Without a seal, a bolus of contrast agent can be
injected through the microcatheter 102 and be released through the
distal end of the microcatheter. Compounds to facilitate clot
removal, accelerate healing of the blood vessel, minimize
reperfusion injury etc. may be delivered through the lumen of the
microcatheter 102 to the area of the clot/infarct region. When the
seal is made, the balloon 100 can be inflated. An additional
constraint/consideration is that the distance between the balloon
100 and the reperfusion member 108 should be short in order to
minimize the chance of interference by a collateral artery during
postconditioning. If another blood vessel were to intersect the
occluded artery, between the clot and the balloon, then the balloon
100 would not be able to cut off blood supply entirely during
postconditioning. In other words, the collateral blood vessel would
not be blocked and would continue supplying blood to the region
even when the balloon was fully inflated. In the preferred
embodiment shown, the distance a is approximately 8 mm and the
distance b is approximately 5 mm.
[0156] Specifications follow for the preferred embodiment shown in
FIGS. 1A, 1B, 3A and 3B. However, a range of specifications and
dimensions may be used.
[0157] The wall thickness of the microcatheter 102 is about 85
.mu.m.
[0158] In the wider part of the microcatheter 102, the gap 126
between the pushwire 106 and the inner lumen of the
microcatheter--if the pushwire is centered within the
microcatheter--is about 150 .mu.m. However, this gap 126 may range
from approximately 50 .mu.m to 300 .mu.m.
[0159] The inner diameter of the wider portion of the microcatheter
102 is approximately 0.018''. However microcatheters having a range
of diameters, for example, approximately 0.014'' to 0.021'' may
also be used. In the narrower part b of the microcatheter, the gap
128 between the pushwire and the inner lumen of the
microcatheter--if the pushwire is centered within the
microcatheter--is about 100 .mu.m. However, this gap may range from
about 30 .mu.m to about 280 .mu.m. The preferred inner diameter of
the narrower portion of microcatheter is approximately 0.002''less
than the inner diameter of the wider portion of microcatheter.
Extrusion is the preferred method to manufacture the
microcatheter.
[0160] FIGS. 4A-4D illustrate steps for using assemblies with a
single-lumen balloon microcatheter and a pushwire-mounted sealing
ring in accordance with some embodiments of the present invention.
The assembly in FIGS. 4A-4D includes a flow modulation member
balloon 100 deflated and flush against the outer wall of the
microcatheter 102 with inflating fluid passages 122. When the
sealing ring 104 is in a first region 400 of the microcatheter 102,
the balloon 100 cannot inflate, fluid can flow through the
microcatheter and into the blood vessel, and the clot-capturing
reperfusion member 108 is constrained, as shown in FIG. 4A. When
the microcatheter is translated proximally 116 so that the sealing
ring is in a second region 402 of the microcatheter, the balloon
100 cannot inflate, fluid can flow through the microcatheter 102
and into the blood vessel, and the clot-capturing reperfusion
member 108 is partially constrained, as shown in FIG. 4B. When the
microcatheter 102 is translated further proximally so that the
sealing ring 104 is in a third region 404, the balloon 100 cannot
inflate, fluid can flow through the microcatheter 102 and into the
blood vessel, and the clot-capturing reperfusion member 108 is
fully deployed, as shown in FIG. 4C. When the microcatheter 102 is
translated even further proximally so that the sealing ring is in
fourth region 406, the balloon can inflate, as shown in FIG.
4D.
[0161] FIGS. 10A and 10B, 12A and 12B, 14A and 14B, 16A and 16B,
19A and 19B, 21A and 21B, 23A and 23B, 26A and 26B, 48A and 48B and
50A and 50B describe in detail the steps for using the assemblies
disclosed in the present specification in connection with different
embodiments of the present invention. As illustrated in FIG. 5,
while the sealing ring 104 is in the narrower region of
microcatheter 102, inflating fluid 500 can be pumped into the
microcatheter and will inflate the balloon 100. In this alignment
of elements, as shown in FIG. 5, fluid will not freely pass from
the microcatheter into the blood vessel, and the clot-capturing
reperfusion member is fully deployed. Additionally, various ports,
connectors (such as Luer locks) and adaptors can be used at the
proximal end of the catheter in a manner enables the device to
deliver fluid in accordance with the present invention.
[0162] This slightly wider microcatheter also creates an ideal
channel to deliver fluids to the infarcted tissue in region of the
clot and/or the clot itself (e.g., contrast agent, agents to treat
reperfusion injury, agents to aid in clot removal. Tissue
plasminogen activator (tPA) could also be applied locally--reducing
the systemic risks of bleeding--and in lower overall quantities.
Agents that may minimize reperfusion injury include, but are not
limited to, cyclosporine, calpain inhibitors, sodium-calcium
Na+/Ca2+ exchange inhibitors, monoclonal antibodies, temperature
reducing agents, or agents that slow cell metabolism. Agents that
may aid in clot removal include, but are not limited to, tissue
plasminogen activator and other agents that aid in dissolving,
dislodging, and/or macerating clots. Agents that may otherwise
benefit the patient's condition include pharmaceuticals or
compounds commonly used for treating clots, preventing restenosis,
intravascular device coatings (e.g., vasodilators, nimodipine,
sirolimus, paclitaxel) and agents that promote the entanglement or
attachment of a clot with a reperfusion member (e.g., fibronectin).
The preferred embodiment will therefore provide an opportunity to
use drugs that may help lessen the ischemic and reperfusion
injuries and/or speed recovery.
[0163] The sealing ring may come in various shapes and dimensions.
The sealing ring need not be shaped so as to resemble a cylinder
with a substantially circular base. As shown in FIG. 6, the sealing
ring 600 is disposed on the pushwire 106 and may be shaped as a
cone in accordance with some embodiments of the present invention.
In this cone shape, the sealing ring 600 may be configured to fit
(either partially or fully) into a corresponding narrow section 602
of the microcatheter.
[0164] FIGS. 7A-7B illustrate, according to some embodiments,
alternative microcatheter designs for preventing the sealing ring
104 from advancing beyond the distal end of the microcatheter. In
both embodiments, the sealing ring 104 includes a forward (distal)
end 702 and a back (proximal) end 704. In FIG. 7A, the distal end
of the microcatheter 700 tapers after the sealing region as
illustrated at region 712. The inside taper of the region 712 is
configured to conform to the distal end 702 of the sealing member.
In FIG. 7B, an additional region 706 with a diameter too narrow to
permit passage of the sealing ring 104 further stabilizes the
blockage, ensuring that the sealing ring will be less likely to
pass through even if force is exerted. The sealing ring may be
designed to not fully enter into a sealing region but instead for
only the distal portion of the sealing ring to contact one or more
narrowing regions of the microcatheter. The microcatheter may have
either sharp or rounded edges on one or more sides, and the slope
of the edges may vary. The microcatheter diameter may taper
linearly, sharply, or gradually. The narrowing regions of the
microcatheter need not be manufactured contiguously. For example, a
tube with a smaller diameter than the microcatheter (or another
ring) may be attached within the microcatheter (in effect,
narrowing the lumen of a distal portion of the microcatheter).
Another example is where the distal end of the balloon wraps around
and into the distal end of the microcatheter to create the narrower
sealing (i.e., ring stopping) portion.
Balloons Compatible with Pushwire-Bearing Sealing Rings
[0165] In all embodiments herein having a balloon, the membrane of
the balloon may be constructed from various materials.
Polypropylene is preferred but other materials may be used,
including, but not limited to, thermoplastic polymers, elastomeric
silicones, latexes, other polymers or a blend thereof (e.g.,
ENGAGE.RTM. polyolefin elastomers available from the Dow Chemical
Company (Midland, Mich.)). To reliably occlude while not damaging
the artery, the balloon is soft, compliant and operated under a
range of low pressures. The balloon may occlude the vessel at
inflation pressures ranging from about 0.1 to 5 atm. The balloon is
preferred to be one-size-fits-all-cerebral-vessels with balloon
diameters ranging from 1 to 5 mm in the inflated state.
Alternatively, various microcatheters may be manufactured with
balloons of different sizes to accommodate a range of occluded
vessel diameters. The target diameters of the different sized
balloons may be about 1 to 5 mm (i.e., different sizes are suitable
for differently sized arteries). The length of the balloon is
preferred to be 10 mm (which, in some embodiments can be short to
improve navigability). However, a range of balloon lengths may be
used (for example from about 5 mm up to about 30 mm).
[0166] The balloon may be coated with various coatings to reduce
friction between the balloon and the vessel and also to avoid
adhesion of thrombus. For example, a hydrophilic coating such as
polytetrafluoroethylene, is preferred.
[0167] Radiopaque marker-bands 124 (illustrated in FIGS. 1A and 1B)
are preferred to be placed near the horizontal extremities of the
balloon. It is preferred to place two marker-bands, one near the
proximal end of the balloon and one near the distal end. In
embodiment of FIGS. 1A and 1B, the marker-bands 124 are around the
microcatheter 102, but within the inner lumen of the balloon 100.
Alternatively, the marker-bands may be embedded within the plastic
wall of the microcatheter. Radiopaque materials may also be
incorporated within the material of the balloon membrane, or used
to coat the balloon. The radiopaque materials aid the operator in
seeing the position, state of expansion, and rate of expansion and
compression of the balloon. Any of these radiopaque marker
configurations can be used with different disclosed embodiments.
Along with saline solution, contrast agent may be part of the
inflating solution so that the inflation of the balloon may be
observed with angiography.
[0168] FIGS. 8-9 illustrate a passage for the flow of inflating
fluid between a catheter 102 and an inflatable flow modulation
member in accordance with some embodiments of the present
invention. In FIG. 8, the passage, illustrated as inflating hole
122, (illustrated in FIGS. 1A, 1B, 3A, 3B) is circular 800 and has
a diameter of, for example, about 100 .mu.m. Other diameters may
also be used including, but not limited to, the range of about 30
.mu.m to 200 .mu.m. More than one hole with similar or differently
sized diameters and shapes may be used. The holes have walls 802
which may be cylindrical, but may also embody some other
configuration, e.g. a tapered configuration may reduce the
likelihood that the clot capture reperfusion member may snag on the
hole 800. FIG. 9 illustrates an alternative embodiment, in which an
elliptical inflating hole 900, so that the smallest diameter is
parallel to the central axis 902 of the microcatheter 102 (so as to
reduce the likelihood of the clot-capturing reperfusion member from
temporarily catching on or jamming in the inflating hole). The
dimensions of the inflating hole shown in FIG. 9 are about 30 .mu.m
at the smallest diameter and about 100 .mu.m at the largest
diameter. In other embodiments, the shape and/or size of the base
of an inflating hole may vary. One or more inflating holes may be
cut into the microcatheter or catheter using methods including, but
not limited to, electron beam drilling, laser drilling, and
classical machining.
[0169] The balloon 100 is attached to the microcatheter 102 in the
attachment regions 130 (illustrated in FIGS. 1A, 1B, 3A, 3B) on
either side of the inflating membrane. The attachment regions 130
are contiguous bands around the microcatheter 102. The attachment
regions keep the inflating solution from escaping from the balloon
100. Many methods may be used to attach the balloon 100 to the
microcatheter 102 (e.g., fusion bonding, ultrasonic welding,
solvent bonding, induction welding, and dielectric welding).
[0170] Embodiments that utilize programmed flow modulation may be
used to standardize manual work and/or to automatically detect and
adjust the pressure in the flow modulation balloon to exert the
desired pressure on the blood vessel walls. Pressure sensing
capabilities make it easier to inflate the balloon according to the
varying radii of different blood vessels. Thus, a balloon flow
modulation system according to some embodiments may be more precise
and responsive, may require less work and judgment on the part of
an operator, and may keep detailed treatment records.
[0171] A multi-port adapter (e.g., a dual port adaptor) may be
attached to the proximal end of the conduit (e.g., a balloon
microcatheter) to receive the inflating fluid. The adapter has a
port for the endovascular devices that can be used to access the
lumen of the microcatheter, as well as a port for attaching a
removable pressure transducer. The transducer is either manually
operated (e.g., by a syringe) or automatically operated pump (e.g.,
peristaltic pump). The pressure transducer will inflate and deflate
the balloon to create postconditioning (sequence of blocking and
restarting blood flow).
[0172] The pressure transducer apparatus could be, for example,
peristaltic pumps such as the Ismatec ICC 3 Channel 8 Roller
Peristaltic Pump (available from Cole-Parmer (Vernon Hills, Ill.)
or the mp6 micropump (available from Bartels Mikrotechnik GmbH,
Munich, Germany). The pump should have a flow rate superior to
about 5 mL-per-minute in order to inflate the balloon in less than
10 seconds.
[0173] A preprogrammed (or programmable) electronic control system
is preferred to control the electronic signals that drive the flow
rate or pressure differential across the transducer according the
desired postconditioning protocol. This electronic control system
is useful because it adds precision to the postconditioning cycles
and convenience (in comparison to manual control of the expansion
and deflation of each cycle). The electronic control system is
preferred to be a freestanding small chip. However, various types
of computers and electronics may also be used. For example, the
Ismatec ICC3 Channel 8 Roller Peristaltic Pump (Cole Parmer, Vernon
Hills, Ill., USA) may be linked with a computer and controlled with
software such as LabVIEW (available from National Instruments,
Austin, Tex., USA).
[0174] Pressure data may be collected, preferably by inserting a
pressure-sensing probe (e.g., a manometer) into a separate port
near the proximal end of the conduit for the inflating fluid (e.g.,
a balloon microcatheter). This pressure data is preferred to be
processed by the electronic control system. If at any time the
pressure exceeds a threshold that may compromise the mechanical
integrity of the balloon or blood vessel, the electronic control
system will cause the pressure transducer to remove inflating fluid
from the balloon and reduce pressure.
Methods of Using Pushwire-Bearing Sealing Rings
[0175] FIGS. 10A and 10B are process flow charts for performing
postconditioning with mechanical thrombectomy (an example of a
technique to achieve reperfusion) in accordance with some
embodiments of the present invention. For example, the steps in
FIGS. 10A and 10B may be applied to assemblies with a single-lumen
balloon catheter and a pushwire bearing a sealing ring.
[0176] In step 1001, a large catheter (e.g., a 6 French catheter)
is inserted and guided, for example, from the femoral artery to the
neck. In step 1002, a guidewire is inserted through the large
catheter and navigated so that its distal end is at a position
distal to the location of the clot, for example, in a cerebral
artery.
[0177] In optional step 1003, an intermediate catheter (e.g., a 5
French catheter) is inserted over the guidewire and advanced so
that its distal end is at a position (e.g., the sphenoidal (M1)
segment of the middle cerebral artery) that is closer to the clot
than the distal end of the large catheter. In the event of
subsequent passes, an intermediate catheter saves time in
navigating a new guidewire from the distal end of the larger
catheter to a position distal to the location of the clot.
[0178] In step 1004, a microcatheter is inserted over the guidewire
and advanced so that its distal end is positioned distal to the
clot. The microcatheter has a distal region in which its internal
diameter decreases. The microcatheter may, but need not, advance
any further than the distal end of the guidewire. In step 1005, the
guidewire is removed from the microcatheter and replaced with a
pushwire. The pushwire has a reperfusion member coupled to its
distal end and a sealing ring proximal to the reperfusion member.
Some reperfusion members (such as those that may have clot-capture
functionality) may have a self-expanding region adapted for
engaging with a clot (i.e., an active region). If using a
clot-capturing reperfusion member, the active region of the
reperfusion member may be advanced within the microcatheter so as
to be adjacent to the clot. Thus, when the microcatheter is
retracted proximally to unsheathe the reperfusion member, as in
step 1006, the active region will expand and engage with the clot.
During all passes with the clot-capturing reperfusion member, the
microcatheter should be sufficiently retracted so that the sealing
ring coupled to the pushwire enters the narrow distal region of the
microcatheter and creates a seal within the microcatheter lumen
proximal to the sealing ring for retaining inflating fluid in the
microcatheter.
[0179] Following step 1006, the status of reperfusion should be
assessed and the elapsed time tracked. The reperfusion status may
be assessed by, for example, injecting a contrast agent (e.g., a
bolus of radiopaque solution) through the large catheter and
performing angiography to view the diffusion of the contrast agent.
Suitable contrast agents may include, but are not limited to,
iothalamate meglumine, diatrizoate meglumine, and other
iodine-containing solutions. If the artery is not reperfused, then
proceed to step 1007 in order to wait and check reperfusion status
again. If reperfusion has occurred then proceed with
postconditioning 1010 if postconditioning has not be already
performed on a prior pass, or step 1011, which consists of
extracting the device to move towards completion of the procedure,
if postconditioning was performed previously.
[0180] In step 1006, if the blood vessel has not been sufficiently
reperfused, then proceed to step 1007 where inflating fluid is
pumped into the single microcatheter lumen, thus inflating the flow
modulation member and occluding the blood vessel. A determined
period of wait-time "t" (e.g., about 5 minutes) is allowed so that
the clot-capturing reperfusion member may expand into and engage
with the clot. After wait time t, the flow modulation member is
deflated and the status of reperfusion is assessed again. If the
blood vessel has not been adequately reperfused, proceed with step
1008 where the microcatheter and pushwire are removed. If a
predetermined maximum number of passes has not yet been completed,
a new pass is initiated in step 1009 with the insertion of a new
guidewire. Steps 1004-1009 are repeated in subsequent passes until
either (1) the predetermined maximum number of passes has been
completed, in which case proceed with step 1013, or (2) the blood
vessel is sufficiently reperfused, in which case proceed with
either step 1010 if postconditioning has not been already performed
or step 1011 if postconditioning was performed previously.
[0181] Therefore, if the blood vessel is sufficiently reperfused
after step 1006 or step 1007, postconditioning will be performed
using the flow modulation member unless postconditioning was
performed on a previous pass. To perform postconditioning, the flow
modulation member (e.g., a balloon) is inflated and deflated in
step 1010 according to a determined series of one or more
postconditioning cycles. Preferred examples of postconditioning
cycles are described in greater detail elsewhere herein.
[0182] According to some embodiments of the present invention, the
balloon is inserted with, attached to, and flush with the external
wall of the microcatheter. The balloon may be inflated and deflated
either by manual or by automatic pumping of inflating fluid in and
out of the microcatheter lumen, which is continuous with the
balloon lumen via inflation holes. When inflating fluid is pumped
through the microcatheter, it flows through the inflation holes in
the microcatheter lumen wall and into the balloon. The balloon
membrane expands against the blood vessel, blocking a substantial
portion of the vessel's lumen. In a preferred embodiment, the
balloon membrane contacts the inner lumen of the blood vessel to
create a complete occlusion of blood flow. The balloon membrane is
flexible so that it will conform to the blood vessel's wall. By
having a blood-flow-occluding balloon in place, a stable
hemodynamic environment is created, which helps minimize the risk
of distal embolization. In some embodiments, this increases the
benefits of postconditioning by controlling when reperfusion first
occurs, so that postconditioning may be performed from the onset of
reperfusion.
[0183] Upon removal of inflating fluid from the microcatheter, the
balloon also empties (i.e., deflates) and gradually resumes its
former shape, once again becoming flush with the external wall of
the microcatheter. Inflating fluid can be removed using, for
example, suction or by unsealing the microcatheter (via moving the
sealing region away from the sealing ring). With deflation, the
occlusion is gradually removed and the blood flow gradually
restored.
[0184] If reperfusion is sufficient but postconditioning has
already been performed on a previous pass, the microcatheter and
pushwire are removed from the body in step 1011. In a given pass,
after unsheathing the clot-capturing reperfusion member in step
1006 the operator should allow the clot-capturing reperfusion
member to expand into the clot until wait time t has elapsed. To
simultaneously remove the microcatheter and pushwire, an operator
may hold the proximal ends of the pushwire and microcatheter
together and translate them proximally until they are completely
withdrawn from the body in accordance with some embodiments. The
clot-capturing reperfusion member is not resheathed in the
microcatheter during its exit from the body, but instead passes,
with the microcatheter and pushwire, within and through the
intermediate catheter (if present) and/or the larger catheter.
Therefore, the intermediate and/or larger catheters remain in place
while the microcatheter and pushwire are removed from the body.
Optionally, suction may be applied through the larger catheter
and/or intermediate catheter to limit the dispersion of secondary
emboli.
[0185] In step 1012, the operator determines whether clot material
has been sufficiently removed by the clot-capturing reperfusion
member. The status of reperfusion may inform this inquiry. Thus, in
some embodiments, the status of reperfusion is assessed by, for
example, injecting a contrast agent through the large catheter and
performing angiography to view the diffusion of the contrast agent.
In some embodiments, the reperfusion member itself is inspected
(e.g., visually) to determine whether the degree of retrieved clot
material is sufficient. Sufficiency may depend on numerous factors
including, but not limited to, changes in perfusion.
[0186] Following step 1012, if a sufficient amount of clot material
has been retrieved, as evidenced by the status of reperfusion, the
procedure is completed and any remaining catheters are removed from
the body according to step 1013. However, if an insufficient amount
of clot material has been retrieved, and if a predetermined maximum
number of passes has not yet been completed, a new pass is
initiated in step 1009 with the insertion of a new guidewire.
Using Electroactive Polymers to Enable Occlusion Using Flow
Modulation Member
[0187] An electroactive polymer (EAP) may be used to perform an
intermediate step that allows for the flow modulation member to
occlude the blood vessel. In some embodiments, the electroactive
polymer is used as a controllable seal for inflating fluid. The
electroactive polymer shown in FIGS. 11A-11B may be used for the
sealing ring 1104. The passage of electric current through the
connectors 1140 and 1142 will reversibly increase the volume of the
sealing ring 1104, including its diameter. When the sealing ring
expands FIGS. 11C-11D, it contacts the walls of the microcatheter
1102 and creates a seal. When using an expandable sealing ring, a
narrower distal diameter 128 (shown in FIGS. 1A and 1B) for the
microcatheter may not be needed.
[0188] Various electroactive polymers may be used, including, but
not limited to, PPy (Polypyrrole), NAFION.RTM., ionic polymer-metal
composites (ionic EAPs) and other materials exhibiting the needed
bending, expanding, contracting, and form changing properties. Two
wires 1140 and 1142 to carry current to and from the electroactive
polymer 1104 may be coated and placed along the pushwire 106 (shown
in FIGS. 1A and 1B). Alternatively, the pushwire itself and/or
internal strands of the pushwire may be used to replace one or both
wires that would have been external to the core of the
pushwire.
[0189] The electroactive sealing ring allows for sealing and
unsealing to be achieved without translation of the microcatheter.
In this way, a channel for delivering beneficial agents can be
created more easily during postconditioning periods when the device
is not occluding.
Methods of Using Electroactive Polymers to Enable Occlusion Using
Flow Modulation Member
[0190] FIGS. 12A and 12B are a process flow chart for performing
postconditioning with mechanical thrombectomy (an example of one of
the various techniques for achieving reperfusion) in accordance
with some embodiments of the present invention. For example, the
steps in FIGS. 12A and 12B may be applied to assemblies with a
single-lumen balloon catheter and a pushwire bearing a
shape-changing sealing ring (such as an EAP sealing ring).
[0191] In step 1201, a large catheter (e.g., a 6 French catheter)
is inserted and guided, for example, from the femoral artery to the
neck. In step 1202, a guidewire is inserted through the large
catheter and navigated so that its distal end is at a position
distal to the location of the clot, for example, in a cerebral
artery.
[0192] In optional step 1203, an intermediate catheter (e.g., a 5
French catheter) is inserted over the guidewire and advanced so
that its distal end is at a position (e.g., the sphenoidal (M1)
segment of the middle cerebral artery) that is closer to the clot
than the distal end of the large catheter, but still proximal to
the clot. In the event of subsequent passes, an intermediate
catheter saves time in navigating a new guidewire from the distal
end of the larger catheter to a position distal to the location of
the clot.
[0193] In step 1204, a microcatheter is inserted over the guidewire
and advanced so that its distal end is at a position distal to the
clot. In step 1205, the guidewire is removed from the microcatheter
and replaced with a pushwire. The pushwire has a reperfusion member
coupled to its distal end and an EAP sealing ring proximal to the
reperfusion member. Some reperfusion members, such as those that
may have clot-capture functionality, may have a self-expanding
region adapted for engaging with a clot (i.e., an "active region").
If using a clot-capturing reperfusion member, the active region of
the reperfusion member may be advanced within the microcatheter so
as to be adjacent to the clot. Thus, when the microcatheter is
retracted proximally to unsheathe the reperfusion member, as in
step 1206, the active region will expand and engage with the clot.
During all passes with a clot-capturing reperfusion member, the
microcatheter should be sufficiently retracted so that the
reperfusion member contacts the clot.
[0194] A control handle ("voltage controller"), containing a
voltage source (e.g., a battery) is affixed to the proximal end of
the pushwire. By affixing the voltage controller, the electrical
connectors from the voltage source join the wires 1140 and 1142
that develop voltage across the EAP as shown in FIGS. 11A-11D. A
switch on the voltage controller is pressed, developing voltage
across the EAP and causing the EAP to swell, thereby creating a
seal between the pushwire and the microcatheter.
[0195] Following step 1206 in FIG. 12A the status of reperfusion
should be assessed and the elapsed time tracked. Reperfusion status
may be assessed by, for example, injecting a contrast agent (e.g.,
a bolus of radiopaque solution) through the large catheter and
performing angiography to view the diffusion of the contrast agent.
Suitable contrast agents may include, but are not limited to,
iothalamate meglumine, diatrizoate meglumine, and other
iodine-containing solutions. If the artery is not reperfused, then
proceed to step 1207 in order to wait and check reperfusion status
again. If reperfusion has occurred then proceed with either (1)
postconditioning 1210, if postconditioning has not been already
performed on a prior pass; or (2) step 1211, which consists of
extracting the microcatheter and pushwire from the body, if
postconditioning was performed previously.
[0196] In step 1206, if the blood vessel has not been sufficiently
reperfused, then proceed to step 1207 where inflating fluid is
pumped into the single-lumen microcatheter, thus inflating the flow
modulation member and occluding the blood vessel. A determined
period of wait-time "t" (e.g., 5 minutes) is allowed so that the
clot-capturing reperfusion member may expand into and engage with
the clot. After wait time t, the flow modulation member is deflated
and the status of reperfusion is assessed again. If the blood
vessel has not been adequately reperfused, proceed with step 1208
where the microcatheter and pushwire are removed. If a
predetermined maximum number of passes has not yet been completed,
a new pass is initiated in step 1209 with the insertion of a new
guidewire. Steps 1204-1209 are repeated in subsequent passes until
either (1) the predetermined maximum number of passes has been
completed, in which case proceed with step 1213, or (2) the blood
vessel is sufficiently reperfused, in which case proceed with
either step 1210 if postconditioning has not been already performed
or step 1211 if postconditioning was performed previously.
[0197] If the blood vessel is sufficiently reperfused after step
1206 or step 1207, postconditioning will be performed using the
flow modulation member unless postconditioning was performed on a
previous pass. If reperfusion is sufficient and postconditioning
has not been performed on a previous pass, the flow modulation
member (e.g., a balloon) is inflated and deflated in step 1210
according to a predetermined series of one or more postconditioning
cycles. Voltage is maintained at least during the parts of the
cycles where the balloon is inflated. The seal can simply be
maintained throughout the postconditioning cycles. To administer
beneficial agents through the microcatheter to the infarct region
or clot, the seal can be temporarily removed by stopping voltage
periodically during postconditioning, for example during the
reperfusion periods within the cycles. Examples of postconditioning
cycles are described in greater detail elsewhere herein.
[0198] According to some embodiments of the present invention, the
balloon is inserted with, attached to, and flush with the external
wall of the microcatheter. The balloon may be inflated and deflated
either by manual or by automatic pumping of inflating fluid in and
out of the microcatheter lumen, which is continuous with the
balloon lumen via inflation holes. When inflating fluid is pumped
through the microcatheter, it flows through the inflation holes in
the catheter lumen wall and into the balloon. The balloon membrane
expands against the blood vessel, blocking a substantial portion of
the vessel's lumen. In a preferred embodiment, the balloon membrane
contacts the inner lumen of the blood vessel to create a complete
occlusion of blood flow. The balloon membrane is flexible so that
it will conform to the blood vessel's wall. By having a blood
flow-occluding balloon in place, a stable hemodynamic environment
is created, which helps minimize the risk of distal embolization.
In some embodiments, this increases the benefits of
postconditioning by controlling when reperfusion first occurs, so
that postconditioning may be performed from the onset of
reperfusion.
[0199] Upon removal of inflating fluid from the microcatheter, the
balloon also empties (i.e., deflates) and gradually resumes its
former shape, once again becoming flush with the external wall of
the microcatheter. Inflating fluid can be removed using suction or
by relaxing the seal. With deflation, the occlusion is gradually
removed and the blood flow gradually restored.
[0200] If reperfusion is sufficient but postconditioning has
already been performed on a previous pass, the microcatheter and
pushwire are removed from the body in step 1211. In a given pass,
after unsheathing the clot-capturing reperfusion member in step
1206 the operator should allow the clot-capturing reperfusion
member to expand into the clot until wait time t has elapsed. To
simultaneously remove the microcatheter and pushwire, an operator
may hold the proximal ends of the pushwire and microcatheter
together and translate them proximally until they are completely
withdrawn from the body in accordance with some embodiments. The
clot-capturing reperfusion member is not resheathed in the
microcatheter during its exit from the body, but instead passes,
along with the microcatheter and pushwire, within and through the
intermediate catheter (if present) and/or the larger catheter.
Therefore, the intermediate and/or larger catheters remain in place
while the microcatheter and pushwire are removed from the body.
Optionally, suction may be applied through the larger catheter
and/or intermediate catheter to limit the dispersion of secondary
emboli.
[0201] In step 1212, an operator determines whether clot material
has been sufficiently removed by the clot-capturing reperfusion
member. The status of reperfusion may inform this inquiry. Thus, in
some embodiments, the status of reperfusion is assessed by, for
example, injecting a contrast agent through the large catheter and
performing angiography to view the diffusion of the contrast agent.
In some embodiments, the reperfusion member itself is inspected
(e.g., visually) to determine whether the degree of retrieved clot
material is sufficient. Sufficiency may depend on numerous factors
including, but not limited to, changes in perfusion.
[0202] Following step 1212, if a sufficient amount of clot material
has been retrieved, as evidenced in some embodiments by the status
of reperfusion, the procedure is completed and any remaining
catheters are removed from the body according to step 1213.
However, if none or an insufficient amount of clot material has
been retrieved, and if a predetermined maximum number of passes has
not yet been completed, a new pass is initiated in step 1209 with
the insertion of a new guidewire.
Intermediate Single-Lumen Balloon Catheters with Microcatheters
Bearing Sealing Rings
[0203] The use of a movable seal disposed within a lumen that has a
sealing region is certainly applicable beyond the
pushwire/microcatheter context. In FIG. 13, for example, a rounded
sealing ring 1304 is attached to a microcatheter 1302. The sealing
region 1340 is on the inner lumen of an intermediate catheter 1308.
The membrane for the balloon 1300 attaches to the intermediate
catheter 1308 in the attachment regions 1330. When the rounded
sealing ring 1304 is placed in the sealing region 1340 of the
intermediate catheter, defined by a polymeric tube that may be made
from the same material as the intermediate catheter 1308 (a
different material may also be used) that creates a narrower lumen,
inflating fluid 500 pushed through the lumen of the intermediate
catheter 1308 will flow through the inflating holes 1322.
[0204] The embodiment shown in FIG. 13 is an assembly composed of a
sealing ring 1304 mounted on a microcatheter 1302 and a single
lumen intermediate catheter 1308, which provides enhanced
navigability and allows for the delivery of the reperfusion member
108 (shown in FIGS. 1A and 1B, etc.) at the location of the clot.
Clots tend to lodge in the Middle Cerebral Artery, where the
vasculature is particularly tortuous. Using a sealing ring design
eliminates the need for an additional lumen on the intermediate
catheter and therefore increases flexibility.
[0205] The preferred length of the sealing ring is about 4 mm.
However, different dimensions for the sealing ring may be used
(e.g. from approximately 2 mm to approximately 10 mm in length).
The diameter of the sealing ring is preferred to be the same as the
inner diameter of the narrower region of the intermediate catheter.
It is anticipated that matching diameters, e.g., about 0.046'',
will provide adequate sealing while minimizing the risk of assembly
jamming. However, different dimensions for the sealing ring may be
used (e.g. from about 0.0350'' to 0.055'' in diameter).
[0206] The sealing ring can be attached to the microcatheter in
many ways, (e.g., solvent bonding, gluing and interference
fitting). In the preferred embodiment, the sealing ring is composed
of the same material as that of the microcatheter; however, other
materials may be used (e.g., silicone, PET, latex, nylon, and
rubber).
[0207] The insert for the narrowing of the lumen can be attached to
the intermediate catheter in many ways, for example: solvent
bonding and interference fitting. In the preferred embodiment the
sealing region insert 1340 in the lumen is composed of the same
material as that of the microcatheter; however, other materials may
be used. The intermediate catheter 1308 and the sealing region
insert 1340 may be manufactured as one part. In this case, the
intermediate catheter would be extruded at the desired diameter,
for example a 4 French inner diameter. The narrower sealing region
1340 may be created by pinching or heat forming such that the both
the inner and outer diameter of the intermediate catheter may be
locally reduced simultaneously.
[0208] There are numerous ways that a sealing ring on the
microcatheter can be used to create a seal that will permit the
clot to pass through the intermediate catheter as well as
facilitate postconditioning. The embodiments above are only
examples.
[0209] The sealing ring allows for both the inflation fluid and
microcatheter to use (or have) a single lumen. In the embodiment
shown in FIG. 13, there is space 1306 between the microcatheter
1302 and the luminal wall of the intermediate catheter 1308 to
allow the inflating fluid 500 (e.g., saline solution) to travel
through and inflate the balloon 1300. Additionally, this space
ensures reduced friction between the microcatheter 1302 and the
intermediate catheter 1308, during the translation of one with
respect to the other. The sealing ring may be positioned proximally
to the portion of the microcatheter that will slide through the
clot before deploying the reperfusion member (e.g. about 25 mm
proximal to the distal tip of the microcatheter). The inner lumen
of the intermediate catheter bears inflating holes 1322 (e.g., two
holes in the embodiment shown) that connect the lumen of the
balloon to the inner lumen 1306 of the intermediate catheter, to
let the inflating fluid reach the cavity of the balloon. When
translated into the narrower portion 1340 of the intermediate
catheter 1308, the sealing ring 1304 creates a seal that prevents
the inflating fluid 500 from flowing passed the sealing ring and
freely out of the distal end of the intermediate catheter. Once the
sealing ring 1304 is advanced into the narrower portion 1340 of the
intermediate catheter 1308, pumping the inflation fluid 500 through
the proximal end of the intermediate catheter will result in the
inflation of the balloon 1300.
[0210] The sealing ring is preferred to be rounded to promote ease
of entering the narrower portion of the intermediate catheter. By
only contacting at one point, friction is minimized and the
microcatheter can pass through the intermediate catheter without
jamming. The sealing ring would only need to re-enter the
intermediate catheter if the microcatheter is pushed too far away
(e.g. beyond the distal end of the intermediate catheter).
[0211] The end of the intermediate catheter may be the same
diameter as the non-sealing areas of the intermediate catheter, as
is illustrated in this embodiment shown in FIG. 13. Having a wider
lumen allows the clot to be drawn into the intermediate catheter
(along with the reperfusion member) with less potential for
resistance.
[0212] The preferred outer diameter shown of the microcatheter is
about 2.3 French. However, microcatheter with diameters ranging
from 1.5 French to 3 French may be used.
Intermediate Catheters Compatible with Microcatheters Bearing
Sealing Rings
[0213] The inner diameter throughout the intermediate catheter may
be the same as the diameter of the sealing ring; however, this is
not the preferred embodiment.
[0214] The narrowed region may be about 4 mm long and its center
located about 22 mm from the distal end of the intermediate
catheter. The region of the microcatheter distal to the sealing
ring 1304 has sufficient length so as to not let the sealing ring
interfere with the clot when positioning the microcatheter
adequately before positioning the reperfusion member adjacent to
the clot.
[0215] Specifications follow for the preferred embodiment shown in
FIG. 13. However a range of specifications may be used: The wall
thickness of the intermediate catheter is about 100 .RTM.m. In the
wider part of the intermediate catheter, the gap 1306 between the
outer diameter of the microcatheter and the inner diameter of the
intermediate catheter--if the microcatheter is centered within the
intermediate catheter--is about 283 .mu.m. However, this gap may
range from approximately 150 .mu.m to 400 .mu.m. The inner diameter
of the wider portion of the intermediate catheter is 4 French.
However, intermediate catheters having a range of diameters, for
example 3 French to 5 French, may also be used.
[0216] This slightly wider intermediate catheter also allows for
two ideal channels to deliver fluids to the infarcted tissue, in
region of the clot and/or the clot itself. With both channels,
medicine can reach this infarct area both during and in between
clot retrieval passes. When the ring is not in the sealing region,
both channels are available. Alternating applications of different
medications may be used. One such fluid is contrast agent. Others
include agents to treat reperfusion injury or help otherwise at the
site of the clot. Tissue plasminogen activator (tPA) could also be
applied locally--reducing the systemic risks of bleeding--and in
lower overall quantities. Agents that may minimize reperfusion
injury include cyclosporine, calpain inhibitors, sodium-calcium
Na+/Ca2+ exchange inhibitors, monoclonal antibodies, temperature
reducing agents, or agents that slow cell metabolism. Agents that
may aid in removing a clot include tissue plasminogen activator and
other agents that aid in dissolving, dislodging, or macerating
clots. Agents that may otherwise benefit the patient's condition
include, but are not limited to, pharmaceuticals or compounds
commonly used for treating clots, preventing restenosis,
intravascular device coatings such as vasodilators, nimodipine,
sirolimus, or paclitaxel. The preferred embodiment will therefore
provide an opportunity to use drugs that may help lessen the
ischemic and reperfusion injuries and/or speed recovery.
[0217] The sealing ring may come in various shapes and dimensions.
The sealing ring need not be shaped so as to resemble an ellipsoid
with a hole through the center for the microcatheter. Indeed, it
may be of numerous shapes.
Balloons Compatible with Microcatheters Bearing Sealing Rings
[0218] In this embodiment, the proximal end of the balloon would be
located about 29 mm from the distal end of the intermediate
catheter, such that it begins proximal to the location of the
sealing holes and extends up to the distal end of the intermediate
catheter. Note that the inflation holes should be proximal to the
sealing region. In the embodiment shown the inflation holes are
located about 26 mm from the distal end of the intermediate
catheter. Positioning the inflation holes toward the proximal end
of the balloon and having a longer balloon, allows the sealing
region to be far enough away from the distal end of the
intermediate catheter so that it does not interfere with the clot
upon retrieval. A major advantage of having the balloon extend to
the distal tip of the intermediate catheter is that the distance
between the balloon and the reperfusion member should be short in
order to minimize the chance of interference by a collateral artery
during postconditioning. If another blood vessel were to intersect
the occluded artery, between the clot and the balloon, then the
balloon would not be able to cut off blood supply entirely during
postconditioning. In other words the collateral blood vessel would
not be blocked and continue supplying blood even when the balloon
was fully inflated.
[0219] In all embodiments herein having a balloon, the membrane of
the balloon may be constructed from various materials.
Polypropylene is preferred but other materials may be used,
including, but not limited to, thermoplastic polymers, elastomeric
silicones, latexes, other polymers or a blend thereof. An example
is ENGAGE.TM. polyolefin elastomers available from the Dow Chemical
Company (Midland, Mich.). To reliably occlude while not damaging
the artery, the balloon is soft, compliant and operated under a
range of low pressures. The balloon may occlude the vessel at
inflation pressures ranging from about 0.1 to 5 atm. The balloon is
preferred to be one-size-fits-all-cerebral-vessels with balloon
diameters ranging from about 1 to 5 mm in the inflated state.
Alternatively, various intermediate may be manufactured with
balloons of different sizes to accommodate a range of occluded
vessel diameters. The target diameters of the different sized
balloons may be 1 to 5 mm (i.e., different sizes for different
diameter arteries). In an embodiment, the length of the balloon
1300 is preferred to be 30 mm (to allow a sufficient wide-diameter
lumen at the distal tip of the intermediate catheter). However, a
range of balloon lengths may be used (for example up to about 50
mm).
[0220] The balloon may be coated with various coatings, both to
reduce friction between the balloon and the vessel and also to
avoid adhesion of thrombus. For example, a hydrophilic coating such
as polytetrafluoroethylene is preferred.
[0221] Radiopaque marker-bands 1324 (shown in FIG. 13) are
preferred to be placed near the extremities of the balloon. It is
preferred to place two marker-bands, one near the proximal end of
the balloon and one near the distal end. In the preferred
embodiment FIG. 13, the marker-bands are around the intermediate
catheter, but within the inner lumen of the balloon. Alternatively,
the marker-bands may be embedded within the plastic wall of the
intermediate catheter. Radiopaque materials may also be
incorporated within the material of the balloon membrane, or used
to coat the balloon. The radiopaque materials will aid the operator
in seeing the position, state of expansion, and rate of expansion
of the balloon.
[0222] The inflating holes 1322 are cylindrical holes with a
circular base and a diameter of about 150 .mu.m. A range of
diameters may also be used (e.g., from approximately 100 m to 400
.mu.m). The inflating holes may be cut into the microcatheter or
catheter using electron beam drilling, laser drilling, classical
machining or other methods.
[0223] The balloon is attached to the microcatheter in the
attachment regions 1330 on either side of the inflating membrane.
The attachment regions may be contiguous bands around the
intermediate catheter. The attachment regions keep the inflating
solution from flowing out of the balloon. Many methods may be used
to attach the balloon to the intermediate catheter (e.g., fusion
bonding, ultrasonic welding, solvent bonding, induction welding,
and dielectric welding).
Methods of Using Intermediate Single-Lumen Balloon Catheters with
Microcatheters Bearing Sealing Rings
[0224] FIGS. 14A and 14B are a process flow chart for performing
postconditioning with mechanical thrombectomy (an example of one of
the various techniques for achieving reperfusion) in accordance
with some embodiments of the present invention. For example, the
steps in FIGS. 14A and 14B may be applied to assemblies with an
intermediate single-lumen balloon catheter with a microcatheter
bearing a sealing ring.
[0225] In step 1401, a large catheter (e.g., a 6 French catheter)
is inserted and guided, for example, from the femoral artery to the
neck. In step 1402, a guidewire is inserted through the large
catheter and navigated so that its distal end is at a position
distal to the location of the clot, for example, in a cerebral
artery.
[0226] In step 1403, an intermediate catheter (e.g., a 5 French
catheter) is inserted over the guidewire and advanced so that its
distal end is at a position (e.g., the sphenoidal (M1) segment of
the middle cerebral artery) that is closer to the clot than the
distal end of the large catheter. The intermediate catheter has a
distal region in which its internal diameter locally decreases. In
the event of subsequent passes, an intermediate catheter saves time
in navigating a new guidewire from the distal end of the larger
catheter to a position distal to the location of the clot.
[0227] In step 1404, a microcatheter is inserted over the guidewire
and advanced so that its distal end is at a position distal to the
clot. The microcatheter may but need not advance any further than
the distal end of the guidewire. In step 1405, the guidewire is
removed from the microcatheter and replaced with a pushwire. The
pushwire has a reperfusion member coupled to its distal end. Some
reperfusion members (such as those that may have clot-capture
functionality) may have a self-expanding region adapted for
engaging with a clot (i.e., an "active region"). If using a
clot-capturing reperfusion member, the active region of the
reperfusion member may be advanced within the microcatheter so as
to be adjacent to the clot. Thus, when the microcatheter is
retracted proximally to unsheathe the reperfusion member, as in
step 1406, the active region will expand and engage with the clot.
During all passes with the clot-capturing reperfusion member, the
microcatheter should be sufficiently retracted so that the sealing
ring coupled to the microcatheter enters the narrow distal region
of the intermediate catheter and creates a seal within the
intermediate catheter lumen around the microcatheter, for retaining
inflating fluid in the intermediate catheter (and balloon on the
intermediate catheter).
[0228] Following step 1406, the status of reperfusion should be
assessed and the elapsed time tracked. The reperfusion status may
be assessed by, for example, injecting a contrast agent (e.g., a
bolus of radiopaque solution) through the large catheter and
performing angiography to view the diffusion of the contrast agent.
Suitable contrast agents may include, but are not limited to,
iothalamate meglumine, diatrizoate meglumine, and other
iodine-containing solutions. If the artery is not reperfused, then
proceed to step 1407 in order to wait and check reperfusion status
again. If reperfusion has occurred then proceed with either (1)
postconditioning step 1410, if postconditioning has not been
already performed on a prior pass; or (2) step 1411, which consists
of extracting the microcatheter and pushwire from the body, if
postconditioning was performed previously. To deliver beneficial
agents during postconditioning through the intermediate catheter,
the seal can be temporarily removed by translating the intermediate
catheter so that the sealing ring is no longer within the
intermediate catheter's sealing region. Agents can be delivered
through the large catheter or microcatheter without the need to
remove a seal.
[0229] In step 1406, if the blood vessel has not been sufficiently
reperfused, then proceed to step 1407 where inflating fluid is
pumped into the intermediate catheter, thus inflating the flow
modulation member and occluding the blood vessel. A determined
period of wait-time "t" (e.g., about 5 minutes) is allowed so that
the clot-capturing reperfusion member may expand into and engage
with the clot. After wait time t, the flow modulation member is
deflated and the status of reperfusion is assessed again. If the
blood vessel has not been adequately reperfused, proceed with step
1408 where the microcatheter and pushwire are removed. If a
predetermined maximum number of passes has not yet been completed,
a new pass is initiated in step 1409 with the insertion of a new
guidewire. Steps 1404-1409 are repeated in subsequent passes until
either (1) the predetermined maximum number of passes has been
completed, in which case proceed with step 1413, or (2) the blood
vessel is sufficiently reperfused, in which case proceed with
either step 1410 if postconditioning has not been already performed
or step 1411 if postconditioning was performed previously.
[0230] If the blood vessel is sufficiently reperfused after step
1406 or step 1407, postconditioning will be performed using the
flow modulation member unless postconditioning was performed on a
previous pass. If reperfusion is sufficient and postconditioning
has not been performed on a previous pass, the flow modulation
member (i.e., balloon) is inflated and deflated in step 1410
according to a determined series of one or more postconditioning
cycles. Preferred examples of postconditioning cycles are described
in greater detail elsewhere herein.
[0231] According to some embodiments of the present invention, the
balloon is inserted with, attached to, and flush with the external
wall of the microcatheter. The balloon may be inflated and deflated
either by manual or by automatic pumping of inflating fluid in and
out of the intermediate catheter lumen, which is continuous with
the balloon lumen via inflation holes. When inflating fluid is
pumped through the intermediate catheter, it flows through the
inflation holes in the catheter lumen wall and into the balloon
lumen. The balloon membrane expands against the blood vessel,
blocking a substantial portion of the vessel's lumen. In a
preferred embodiment, the balloon membrane contacts the inner lumen
of the blood vessel to create a complete occlusion of blood flow.
The balloon membrane is flexible so that it will conform to the
blood vessel's wall. By having a blood-flow-occluding balloon in
place, a stable hemodynamic environment is created, which helps
minimize the risk of distal embolization. In some embodiments, this
increases the benefits of postconditioning by controlling when
reperfusion first occurs, so that postconditioning may be performed
from the onset of reperfusion.
[0232] Upon removal of inflating fluid from the microcatheter, the
balloon also empties (i.e., deflates) and gradually resumes its
former shape, once again becoming flush with the external wall of
the microcatheter. Inflating fluid can be removed using suction or
by unsealing the intermediate catheter (via moving the sealing
region away from the sealing ring). With deflation, the occlusion
is gradually removed and the blood flow gradually restored.
[0233] If reperfusion is sufficient but postconditioning has
already been performed on a previous pass, the microcatheter and
pushwire are removed from the body in step 1411. In a given pass,
after unsheathing the clot-capturing reperfusion member in step
1406 the operator should allow the clot-capturing reperfusion
member to expand into the clot until wait time t has elapsed. To
simultaneously remove the microcatheter and pushwire, an operator
may hold the proximal ends of the pushwire and microcatheter
together and translate them proximally until they are completely
withdrawn from the body in accordance with some embodiments. The
clot-capturing reperfusion member is not resheathed in the
microcatheter during its exit from the body, but instead passes,
along with the microcatheter and pushwire, within and through the
intermediate catheter and the larger catheter. Therefore, the
intermediate catheter and large catheter remain in place while the
microcatheter and pushwire are removed from the body. Optionally,
suction may be applied through the larger catheter and/or
intermediate catheter to limit the dispersion of secondary
emboli.
[0234] In step 1412, an operator determines whether clot material
has been sufficiently removed by the clot-capturing reperfusion
member. The status of reperfusion may inform this inquiry. Thus, in
some embodiments, the status of reperfusion is assessed by, for
example, injecting a contrast agent through the large catheter or
intermediate catheter and performing angiography to view the
diffusion of the contrast agent. In some embodiments, the
reperfusion member itself is inspected (e.g., visually) to
determine whether the degree of retrieved clot material is
sufficient. Sufficiency may depend on numerous factors including,
but not limited to, changes in perfusion.
[0235] Following step 1412, if a sufficient amount of clot material
has been retrieved, as evidenced in some embodiments by the status
of reperfusion, the procedure is completed and any remaining
catheters are removed from the body according to step 1413.
However, if none or an insufficient amount of clot material has
been retrieved, and if a predetermined maximum number of passes has
not yet been completed, a new pass is initiated in step 1409 with
the insertion of a new guidewire.
Intermediate Single-Lumen Balloon Catheters with Electroactive
Sealing Members
[0236] Another example of using an electroactive polymer (EAP) in
an enabling step for the flow modulation member is for creating a
seal for inflating fluid. Such seals can be between various
elements. One such embodiment that will be discussed below is
between a microcatheter and an intermediate catheter. The
intermediate single-lumen balloon catheters compatible with
microcatheters bearing sealing rings rely on translation to effect
a complete seal. In contrast, electricity can be used instead of
movement to create the seal. Use of EAPs, for example, is one way
to use electricity to control sealing FIGS. 15A-15B.
[0237] In the illustrated example of an embodiment, an
electroactive ring 1504 constricts (as illustrated in FIG. 15A)
when voltage is developed across the material and it is
"activated." When constricting, the EAP pulls the membrane 1544
inward. The membrane contacts the microcatheter 1502, creating a
seal. With the seal in place, inflating solution 500 can be pumped
into the lumen 1506 of the intermediate catheter, inflating the
balloon (starting about 2 mm 1546 proximal to the distal end of the
intermediate catheter and spanning about 11 mm 1548) on the
intermediate catheter and causing occlusion of the vessel. The
balloon (which can be similar in configuration and dimensions as
previously described) is attached to the catheter at 1530, forming
a fluid tight seal between the catheter and the balloon along the
circumference of the catheter. In the illustrated embodiment, the
balloon is attached at a proximal end and a distal end of the
balloon membrane.
[0238] The embodiment of the intermediate catheter depicted has a
flexible distal segment 1544 starting at about 3 mm proximal to the
distal end of the intermediate catheter and spanning 7 mm 1550 in
length. This segment is thinner or is made of material that is more
flexible than that of the majority of the intermediate catheter
1508. In the illustrated embodiment the EAP ring 1504 is about 3 mm
long (i.e., 1544 in the illustration) and is placed centrally on
the outside of the more flexible catheter wall segment 1544. The
EAP ring constricts as illustrated in FIG. 15A when voltage is
developed across. When electric current is applied, the EAP ring
1504 brings the flexible intermediate catheter segment into contact
with the outer surface of the microcatheter, creating a seal and
allowing the balloon on the intermediate catheter to inflate. When
external voltage ceases, the EAP ring relaxes, and the inner
diameter of the flexible region returns to its resting dimensions,
thereby not interfering with removal of the reperfusion member and
any potential thrombus.
[0239] The EAP band shown in FIGS. 15A and 15B is about 100 .mu.m
in height so that it does not interfere with navigability and does
not significantly increase the overall diameter of the intermediate
catheter.
[0240] The inner diameter of the EAP will contract from
approximately the inner diameter of the intermediate catheter (3.1
French if a 4 French catheter is used) to the outer diameter of the
microcatheter (for example 2.1 French).
[0241] Small wires 1540 and 1542 (illustrated in FIGS. 15A, 15B)
are embedded in the intermediate catheter or run along the outside
of the intermediate catheter to carry voltage to and from the EAP.
The electrically controlled seal may be made of various materials
with suitable constricting, bending or swelling properties. For
example the EAP may include PPy (Polypyrrole), NAFION.RTM., and
ionic polymer-metal composites (ionic EAPs). Other numbers
designate similar elements described in previous embodiments with a
prefix 15 (e.g. the radiopaque markers introduced in FIGS. 1A and
11B as 124 are indicated by 1524.
Methods of Using Intermediate Single-Lumen Balloon Catheters with
Electroactive Sealing Members
[0242] FIGS. 16A and 16B are process flow charts for performing
postconditioning with mechanical thrombectomy (an example of one of
the various techniques for achieving reperfusion) in accordance
with some embodiments of the present invention. For example, the
steps in FIGS. 16A and 16B may be applied to assemblies with a
single-lumen intermediate balloon catheter and a microcatheter
bearing an expandable EAP sealing ring.
[0243] In step 1601, a large catheter (e.g., a 6 French catheter)
is inserted and guided, for example, from the femoral artery to the
neck. In step 1602, a guidewire is inserted through the large
catheter and navigated so that its distal end is at a position
distal to the location of the clot, for example, in a cerebral
artery.
[0244] In step 1603, an intermediate single-lumen balloon catheter
(e.g., a 5 French catheter) is inserted over the guidewire and
advanced so that its distal end is at a position (e.g., the
sphenoidal (M1) segment of the middle cerebral artery) that is
closer to the clot than the distal end of the large catheter. In
the event of subsequent passes, the intermediate single-lumen
balloon catheter saves time in navigating a new guidewire from the
distal end of the larger catheter to a position distal to the
location of the clot.
[0245] In step 1604, a microcatheter is inserted over the guidewire
and advanced so that its distal end is at a position distal to the
clot. In step 1605, the guidewire is removed from the microcatheter
and replaced with a pushwire. The pushwire has a reperfusion member
coupled to its distal end and an EAP sealing ring proximal to the
reperfusion member. Some reperfusion members (such as those that
may have clot-capture functionality) may have a self-expanding
region adapted for engaging with a clot (i.e., an "active region").
If using a clot-capturing reperfusion member, the active region of
the reperfusion member may be advanced within the microcatheter so
as to be adjacent to the clot. Thus, when the microcatheter is
retracted proximally to unsheathe the reperfusion member, as in
step 1606, the active region will expand and engage with the clot.
During all passes with a clot-capturing reperfusion member, the
microcatheter should be sufficiently retracted so that the
reperfusion member contacts the clot. A control handle ("voltage
controller"), containing a voltage source such as a battery, is
affixed to the proximal end of the pushwire. By affixing the
voltage controller, the electrical connectors from the voltage
source join the wires 1540 and 1542 that develop voltage across the
EAP. A switch on the voltage controller is pressed, developing
voltage across the EAP and causing the EAP to swell, thereby
creating a seal between the microcatheter and the intermediate
catheter.
[0246] Following step 1606, the status of reperfusion should be
assessed and the elapsed time tracked. The reperfusion status may
be assessed by, for example, injecting a contrast agent (e.g., a
bolus of radiopaque solution) through the large catheter and
performing angiography to view the diffusion of the contrast agent.
Suitable contrast agents may include, but are not limited to,
iothalamate meglumine, diatrizoate meglumine, and other
iodine-containing solutions. If the artery is not reperfused, then
proceed to step 1607 in order to wait and check reperfusion status
again. If reperfusion has occurred then proceed with either (1)
postconditioning 1610, if postconditioning has not been already
performed on a prior pass, or (2) step 1611, which consists of
extracting the microcatheter and pushwire from the body, if
postconditioning was performed previously. To administer beneficial
agents through the intermediate catheter to the infarct region or
clot, the seal can be temporarily removed by stopping voltage
periodically during postconditioning, for example during the
reperfusion periods within the cycles. Examples of postconditioning
cycles are described in greater detail elsewhere herein. Agents can
be delivered through the large catheter and microcatheter without
the need to remove a seal.
[0247] In step 1606, if the blood vessel has not been sufficiently
reperfused, then proceed to step 1607 where inflating fluid is
pumped into the intermediate catheter lumen, thus inflating the
flow modulation member and occluding the blood vessel. A determined
period of wait-time "t" (e.g., about 5 minutes) is allowed so that
the clot-capturing reperfusion member may expand into and engage
with the clot. After wait time t, the flow modulation member is
deflated and the status of reperfusion is assessed again. If the
blood vessel has not been adequately reperfused, proceed with step
1608 where the microcatheter and pushwire are removed. If a
predetermined maximum number of passes has not yet been completed,
a new pass is initiated in step 1609 with the insertion of a new
guidewire. Steps 1604-1609 are repeated in subsequent passes until
either (1) the predetermined maximum number of passes has been
completed, in which case proceed with step 1613, or (2) the blood
vessel is sufficiently reperfused, in which case proceed with
either step 1610 if postconditioning has not been already performed
or step 1611 if postconditioning was performed previously.
[0248] If the blood vessel is sufficiently reperfused after step
1606 or step 1607, postconditioning will be performed using the
flow modulation member unless postconditioning was performed on a
previous pass. If reperfusion is sufficient and postconditioning
has not been performed on a previous pass, the flow modulation
member (i.e., a balloon) is inflated and deflated in step 1610
according to a determined series of one or more postconditioning
cycles. Voltage is maintained at least during the parts of the
cycles where the balloon is inflated. The seal can simply be
maintained throughout the postconditioning cycles. To administer
beneficial agents through the microcatheter to the infarct region
or clot, the seal can temporarily be removed by stopping voltage
periodically during postconditioning, for example during the
reperfusion periods within the cycles. Examples of postconditioning
cycles are described in greater detail elsewhere herein.
[0249] According to some embodiments of the present invention, the
balloon is inserted with, attached to, and flush with the external
wall of the microcatheter. The balloon may be inflated and deflated
either by manual or by automatic pumping of inflating fluid in and
out of the intermediate catheter lumen, which is continuous with
the balloon lumen via inflation holes. When inflating fluid is
pumped through the intermediate catheter, it flows through the
inflation holes in the catheter lumen wall and into the balloon.
The balloon membrane expands against the blood vessel, blocking a
substantial portion of the vessel's lumen. In a preferred
embodiment, the balloon membrane contacts the inner lumen of the
blood vessel to create a complete occlusion of blood flow. The
balloon membrane is flexible so that it will conform to the blood
vessel's walls. By having a blood flow-occluding balloon in place,
a stable hemodynamic environment is created, which helps minimize
the risk of distal embolization. In some embodiments, this
increases the benefits of postconditioning by controlling when
reperfusion first occurs, so that postconditioning may be performed
from the onset of reperfusion.
[0250] Upon removal of inflating fluid from the microcatheter, the
balloon also empties (i.e., deflates) and gradually resumes its
former shape, once again becoming flush with the external wall of
the intermediate catheter. Inflating fluid can be removed using
suction or by relaxing the seal. With deflation, the occlusion is
gradually removed and the blood flow gradually restored.
[0251] If reperfusion is sufficient but postconditioning has
already been performed on a previous pass, the microcatheter and
pushwire are removed from the body in step 1611. In a given pass,
after unsheathing the clot-capturing reperfusion member in step
1606 the operator should allow the clot-capturing reperfusion
member to expand into the clot until wait time t has elapsed. To
simultaneously remove the microcatheter and pushwire, an operator
may hold the proximal ends of the pushwire and microcatheter
together and translate them proximally until they are completely
withdrawn from the body in accordance with some embodiments. The
clot-capturing reperfusion member is not resheathed in the
microcatheter during its exit from the body, but instead passes,
along with the microcatheter and pushwire, within and through the
intermediate catheter and larger catheter. Therefore, the
intermediate and large catheters remain in place while the
microcatheter and pushwire are removed from the body. Optionally,
suction may be applied through the large catheter and/or
intermediate catheter to limit the dispersion of secondary
emboli.
[0252] In step 1612, an operator determines whether clot material
has been sufficiently removed by the clot-capturing reperfusion
member. The status of reperfusion may inform this inquiry. Thus, in
some embodiments, the status of reperfusion is assessed by, for
example, injecting a contrast agent through the large catheter and
performing angiography to view the diffusion of the contrast agent.
In some embodiments, the reperfusion member itself is inspected
(e.g., visually) to determine whether the degree of retrieved clot
material is sufficient. Sufficiency may depend on numerous factors
including, but not limited to, changes in perfusion.
[0253] Following step 1612, if a sufficient amount of clot material
has been retrieved, as evidenced in some embodiments by the status
of reperfusion, the procedure is completed and any remaining
catheters are removed from the body according to step 1613.
However, if none or an insufficient amount of clot material has
been retrieved, and if a predetermined maximum number of passes has
not yet been completed, a new pass is initiated in step 1609 with
the insertion of a new guidewire.
Other Single-Lumen Balloon Catheter Embodiments of a Flow
Modulation Member with Passive Sealing Mechanisms
[0254] Alternatively, the lumen of the microcatheter may be tapered
at its distal tip such that the distal tip creates a seal against
the pushwire (herein referred to as a "sealing tip"). FIG. 17
illustrates a microcatheter with a sealing tip according to some
embodiments of the present invention. The sealing tip 1700 may be
constructed from an elastic material that can expand to accommodate
the compressed clot-capturing reperfusion member but then contract
(facilitated by bending in region 1704), after the clot-capturing
reperfusion member passes through, to create a seal where the
region of the flexible tip 1702 contacts the pushwire and allow for
inflation of the balloon. The tip widens when pushed by the
reperfusion member. An example of such material is silicon rubber.
The embodiment shown in FIG. 17 is but one example. In FIG. 17, the
flexible tip 1700 is a single part that goes over and attaches, in
region 1706, to the microcatheter. The tip is secured around the
distal end of the microcatheter. FIG. 17 features a tip that
extends beyond the distal edge of the microcatheter. The same
reference numerals are used for elements described in earlier
embodiments.
[0255] There are various ways to build a flexible tipped
microcatheter. Two such embodiments are illustrated in FIGS. 17-18.
FIG. 18 creates a flexible sealing region by having a spongy
material 1800 inside of tip of the microcatheter. One example of a
class of materials that may be used is shape memory polyurethanes.
The spongy material compresses against the microcatheter walls to
allow the reperfusion member to pass through and then hugs the
microcatheter to create a seal. The same reference numerals are
used for elements described in earlier embodiments.
[0256] In flexible tipped embodiments, it is preferred to have a
clot-capturing reperfusion member that is closed at its distal end,
in order to present a streamlined insertion profile to the sealing
tip.
Methods of Using Other Single-Lumen Balloon Catheter Embodiments of
a Flow Modulation Member with Passive Sealing Mechanisms
[0257] FIGS. 19A and 19B are process flow charts for performing
postconditioning with mechanical thrombectomy (an example of one of
the various techniques for achieving reperfusion) in accordance
with some embodiments of the present invention. For example, the
steps in FIGS. 19A and 19B may be applied to assemblies with
single-lumen balloon catheter embodiments of a flow modulation
member that employs sealing mechanisms that are passive in their
method of operation.
[0258] In step 1901, a large catheter (e.g., a 6 French catheter)
is inserted and guided, for example, from the femoral artery to the
neck. In step 1902, a guidewire is inserted through the large
catheter and navigated so that its distal end is at a position
distal to the location of the clot, for example, in a cerebral
artery.
[0259] In optional step 1903, an intermediate catheter (e.g., a 5
French catheter) is inserted over the guidewire and advanced so
that its distal end is at a position (e.g., the sphenoidal (M1)
segment of the middle cerebral artery) that is closer to the clot
than the distal end of the large catheter. In the event of
subsequent passes, an intermediate catheter saves time in
navigating a new guidewire from the distal end of the large
catheter to a position distal to the location of the clot.
[0260] In step 1904, a microcatheter is inserted over the guidewire
and advanced so that its distal end is at a position distal to the
clot. In step 1905, the guidewire is removed from the microcatheter
and replaced with a pushwire. The pushwire has a reperfusion member
coupled to its distal end. Some reperfusion members (such as those
that may have clot-capture functionality) may have a self-expanding
region adapted for engaging with a clot (i.e., an "active region").
If using a clot-capturing reperfusion member, the active region of
the reperfusion member may be advanced within the microcatheter so
as to be adjacent to the clot. Thus, when the microcatheter is
retracted proximally to unsheathe the reperfusion member, as in
step 1906, the active region will expand and engage with the clot.
During all passes with a clot-capturing reperfusion member, the
microcatheter should be sufficiently retracted so that the
reperfusion member contacts the clot.
[0261] Following step 1906, the status of reperfusion should be
assessed and the elapsed time tracked. The reperfusion status may
be assessed by, for example, injecting a contrast agent (e.g., a
bolus of radiopaque solution) through the large catheter and
performing angiography to view the diffusion of the contrast agent.
Suitable contrast agents may include, but are not limited to,
iothalamate meglumine, diatrizoate meglumine, and other
iodine-containing solutions. If the artery is not reperfused, then
proceed to step 1907 in order to wait and check reperfusion status
again. If reperfusion has occurred then proceed with either (1)
postconditioning 1910, if postconditioning has not been already
performed on a prior pass; or (2) step 1911, which consists of
extracting the microcatheter and pushwire from the body, if
postconditioning was performed previously. Beneficial agents may be
delivered during postconditioning or other times through lumens
that are not sealed.
[0262] In step 1906, if the blood vessel has not been sufficiently
reperfused, then proceed to step 1907 where inflating fluid is
pumped into the single-lumen microcatheter, thus inflating the flow
modulation member and occluding the blood vessel. A determined
period of wait-time "t" (e.g., about 5 minutes) is allowed so that
the clot-capturing reperfusion member may expand into and engage
with the clot. After wait time t, the flow modulation member is
deflated and the status of reperfusion is assessed again. If the
blood vessel has not been adequately reperfused, proceed with step
1908 where the microcatheter and pushwire are removed. If a
predetermined maximum number of passes has not yet been completed,
a new pass is initiated in step 1909 with the insertion of a new
guidewire. Steps 1904-1909 are repeated in subsequent passes until
either (1) the blood vessel is sufficiently reperfused, in which
case proceed with either step 1910 if postconditioning has not been
already performed or step 1911 if postconditioning was performed
previously, or (2) the predetermined maximum number of passes has
been completed, in which case proceed with step 1913.
[0263] If the blood vessel is sufficiently reperfused after step
1906 or step 1907, postconditioning will be performed using the
flow modulation member unless postconditioning was performed on a
previous pass. If reperfusion is sufficient and postconditioning
has not been performed on a previous pass, the flow modulation
member (i.e., a balloon) is inflated and deflated in step 1910
according to a determined series of one or more postconditioning
cycles. The flow modulation member can be inflated without the
operator performing additional functions to create a seal. Examples
of postconditioning cycles are described in greater detail
elsewhere herein.
[0264] According to some embodiments of the present invention, the
balloon is inserted with, attached to, and flush with the external
wall of the microcatheter. The balloon may be inflated and deflated
either by manual or by automatic pumping of inflating fluid in and
out of the microcatheter lumen, which is continuous with the
balloon lumen via inflation holes. When inflating fluid is pumped
through the microcatheter, it flows through the inflation holes in
the catheter lumen wall and into the balloon. The balloon membrane
expands against the blood vessel, blocking a substantial portion of
the vessel's lumen. In a preferred embodiment, the balloon membrane
contacts the inner lumen of the blood vessel to create a complete
occlusion of blood flow. The balloon membrane is flexible so that
it will conform to the blood vessel's walls. By having a blood
flow-occluding balloon in place, a stable hemodynamic environment
is created, which helps minimize the risk of distal embolization.
In some embodiments, this increases the benefits of
postconditioning by controlling when reperfusion first occurs, so
that postconditioning may be performed from the onset of
reperfusion.
[0265] Upon removal of inflating fluid from the microcatheter, the
balloon also empties (i.e., deflates) and gradually resumes its
former shape, once again becoming flush with the external wall of
the microcatheter. Inflating fluid can be removed by suction. With
deflation, the occlusion is gradually removed and the blood flow
gradually restored.
[0266] If reperfusion is sufficient but postconditioning has
already been performed on a previous pass, the microcatheter and
pushwire are removed from the body in step 1911. In a given pass,
after unsheathing the clot-capturing reperfusion member in step
1906 the operator should allow the clot-capturing reperfusion
member to expand into the clot until wait time t has elapsed. To
simultaneously remove the microcatheter and pushwire, an operator
may hold the proximal ends of the pushwire and microcatheter
together and translate them proximally until they are completely
withdrawn from the body in accordance with some embodiments. The
clot-capturing reperfusion member is not resheathed in the
microcatheter during its exit from the body, but instead passes,
along with the microcatheter and pushwire, within and through the
intermediate catheter (if present) and/or the larger catheter.
Therefore, the intermediate and/or larger catheters remain in place
while the microcatheter and pushwire are removed from the body.
Optionally, suction may be applied through the larger catheter
and/or intermediate catheter to limit the dispersion of secondary
emboli.
[0267] In step 1912, an operator determines whether clot material
has been sufficiently removed by the clot-capturing reperfusion
member. The status of reperfusion may inform this inquiry. Thus, in
some embodiments, the status of reperfusion is assessed by, for
example, injecting a contrast agent through the large catheter and
performing angiography to view the diffusion of the contrast agent.
In some embodiments, the reperfusion member itself is inspected
(e.g., visually) to determine whether the degree of retrieved clot
material is sufficient. Sufficiency may depend on numerous factors
including, but not limited to, changes in perfusion.
[0268] Following step 1912, if a sufficient amount of clot material
has been retrieved, as evidenced in some embodiments by the status
of reperfusion, the procedure is completed and any remaining
catheters are removed from the body according to step 1913.
However, if none or an insufficient amount of clot material has
been retrieved, and if a predetermined maximum number of passes has
not yet been completed, a new pass is initiated in step 1909 with
the insertion of a new guidewire.
Multiple-Lumen Balloon Embodiments of a Flow Modulation Member
Double-Lumen Balloon Microcatheters
[0269] As illustrated in FIGS. 20A and 20B, a double lumen balloon
microcatheter may be used in lieu of the single-lumen balloon
microcatheter previously described. In this case, the profile of
the inner lumen 2000 will be constant i.e. constant inner diameter.
Here, the inflating solution 500 would have its own dedicated lumen
2006 within the walls 2008 and 2010 of the microcatheter. The
inflating solution would not come into contact with the pushwire
106 or reperfusion member 108. Radiopaque markers 2024 delineate
the extremities of the balloon, as illustrated in FIG. 20B.
[0270] In the preferred embodiment for a double lumen balloon
microcatheter FIGS. 20A, 20B, there are separate coaxial lumens
20C, 20D and 20E. The lumen for the inflating solution 2006
("inflating lumen") in the embodiment shown is narrower than the
lumen 2000 for the pushwire. In the embodiment depicted in FIGS.
20A, 20B, the diameter of the inner lumen is about 0.018'', the
inner wall 2008 and outer wall 2010 are about 85 .mu.m thick, and
the gap between the two walls is about 50 .mu.m. These dimensions
are examples and may vary.
[0271] The outer diameter of the outer wall 2010 is preferred to be
about 0.035'' but may vary from about 0.021'' to 0.050''. Inflating
holes 2002 in the outer wall 2010 of the microcatheter connect the
lumen used for the inflating solution 500 to the balloon 2004.
Rigidity in the longitudinal direction is important to avoid
wrinkling (a unequal longitudinal translation between the two
lumens, which may create a wavy surface). Therefore, there is a
connection 2012 between the two lumens in FIG. 20D. In other
embodiments, the two lumens are largely free-floating FIG. 20C.
They may be connected at the proximal and distal ends and/or
connected intermittently (e.g. having a connection 2012 of length
about 2 mm repeatedly positioned once every about 5 cm).
[0272] The intermittent connections serve to prevent wrinkling
while minimizing rigidity. The intermittent connections need not be
arranged in a parallel line with respect to the central axis. To
have even rigidity in all directions the intermittent connections
may be distributed in various patterns (e.g. random, helical, every
120 degrees etc.). The intermittent connections may be created by
first manufacturing two separate tubes and then using induction
welding to attach the outer tube to the inner tube at various
points. In this case, the outer tube may be slightly deformed (e.g.
pushed inward) at the locations where induction welding has been
used. In other embodiments, there are three or more separate lumens
as illustrated in FIG. 20E. The preferred method for manufacturing
the double lumen balloon catheter is extrusion.
[0273] The method of inflation of the balloon on a double lumen
catheter, manually or by pump, is more straightforward than in the
single lumen-sealing ring embodiment. A pressure transducer is
connected to one of the ports connected to the proximal end of the
inflating lumen. Saline solution--or another inflating fluid, which
may contain contrast agent--is pushed through the inflating lumen.
As a consequence, the pressure of the inflating fluid increases,
inflating fluid goes through the inflating holes, and the balloon
inflates. No locking is required, as with the ring design, to
enable inflation. The method for operation and postconditioning is
similar to that for the other balloons described, such as the
single-lumen balloon with a sealing ring, except there is no
sealing ring and therefore a step to lock the sealing ring would
not be needed.
Methods of Using Double-Lumen Balloon Microcatheters
[0274] FIGS. 21A and 21B are a process flow chart for performing
postconditioning with mechanical thrombectomy (an example of one of
the various techniques for achieving reperfusion) in accordance
with some embodiments of the present invention. For example, the
steps in FIGS. 21A and 21B may be applied to assemblies with
double-lumen balloon microcatheter embodiments of a flow modulation
member.
[0275] In step 2101, a large catheter (e.g., a 6 French catheter)
is inserted and guided, for example, from the femoral artery to the
neck. In step 2102, a guidewire is inserted through the large
catheter and navigated so that its distal end is at a position
distal to the location of the clot, for example, in a cerebral
artery.
[0276] In optional step 2103, an intermediate catheter (e.g., a 5
French catheter) is inserted over the guidewire and advanced so
that its distal end is at a position (e.g., the sphenoidal (M1)
segment of the middle cerebral artery) that is closer to the clot
than the distal end of the large catheter. In the event of
subsequent passes, an intermediate catheter saves time in
navigating a new guidewire from the distal end of the large
catheter to a position distal to the location of the clot.
[0277] In step 2104, a microcatheter is inserted over the guidewire
and advanced so that its distal end is at a position distal to the
clot. In step 2105, the guidewire is removed from the microcatheter
and replaced with a pushwire. The pushwire has a reperfusion member
coupled to its distal end. Some reperfusion members (such as those
that may have clot-capture functionality) may have a self-expanding
region adapted for engaging with a clot (i.e., an "active region").
If using a clot-capturing reperfusion member, the active region of
the reperfusion member may be advanced within the microcatheter so
as to be adjacent to the clot. Thus, when the microcatheter is
retracted proximally to unsheathe the reperfusion member, as in
step 2106, the active region will expand and engage with the clot.
During all passes with a clot-capturing reperfusion member, the
microcatheter should be sufficiently retracted so that the
reperfusion member contacts the clot.
[0278] Following step 2106, the status of reperfusion should be
assessed and the elapsed time tracked. The reperfusion status may
be assessed by, for example, injecting a contrast agent (e.g., a
bolus of radiopaque solution) through the large catheter and
performing angiography to view the diffusion of the contrast agent.
Suitable contrast agents may include, but are not limited to,
iothalamate meglumine, diatrizoate meglumine, and other
iodine-containing solutions. If the artery is not reperfused, then
proceed to step 2107 in order to wait and check reperfusion status
again. If reperfusion has occurred then proceed with either (1)
postconditioning 2110, if postconditioning has not been already
performed on a prior pass; or (2) step 2111, which consists of
extracting the microcatheter and pushwire from the body, if
postconditioning was performed previously. Beneficial agents may be
delivered during postconditioning or other times through lumens
that lead to the artery.
[0279] In step 2106, if the blood vessel has not been sufficiently
reperfused, then proceed to step 2107 where inflating fluid is
pumped into the inflation lumen of the double-lumen microcatheter,
thus inflating the flow modulation member and occluding the blood
vessel. A determined period of wait-time "t" (e.g., about 5
minutes) is allowed so that the clot-capturing reperfusion member
may expand into and engage with the clot. After wait time t, the
flow modulation member is deflated and the status of reperfusion is
assessed again. If the blood vessel has not been adequately
reperfused, proceed with step 2108 where the microcatheter and
pushwire are removed. If a predetermined maximum number of passes
has not yet been completed, a new pass is initiated in step 2109
with the insertion of a new guidewire. Steps 2104-2109 are repeated
in subsequent passes until either (1) the blood vessel is
sufficiently reperfused, in which case proceed with either step
2110 if postconditioning has not been already performed or step
2111 if postconditioning was performed previously, or (2) the
predetermined maximum number of passes has been completed, in which
case proceed with step 2113.
[0280] If the blood vessel is sufficiently reperfused after step
2106 or step 2107, postconditioning will be performed using the
flow modulation member unless postconditioning was performed on a
previous pass. If reperfusion is sufficient and postconditioning
has not been performed on a previous pass, the flow modulation
member (i.e., a balloon) is inflated and deflated in step 2110
according to a determined series of one or more postconditioning
cycles. In contrast to some other embodiments, the flow modulation
member can be inflated without the operator performing additional
functions to create a seal. Examples of postconditioning cycles are
described in greater detail elsewhere herein.
[0281] According to some embodiments of the present invention, the
balloon is inserted with, attached to, and flush with the external
wall of the microcatheter. The balloon may be inflated and deflated
either by manual or by automatic pumping of inflating fluid in and
out of the inflation lumen of the microcatheter, which is
continuous with the balloon lumen via inflation holes. When
inflating fluid is pumped through the inflation lumen of the
microcatheter, it flows through the inflation holes and into the
balloon. The balloon membrane expands against the blood vessel,
blocking a substantial portion of the vessel's lumen. In a
preferred embodiment, the balloon membrane contacts the inner lumen
of the blood vessel to create a complete occlusion of blood flow.
The balloon membrane is flexible so that it will conform to the
blood vessel's walls. By having a blood flow-occluding balloon in
place, a stable hemodynamic environment is created, which helps
minimize the risk of distal embolization. In some embodiments, this
increases the benefits of postconditioning by controlling when
reperfusion first occurs, so that postconditioning may be performed
from the onset of reperfusion.
[0282] Upon removal of inflating fluid from the microcatheter, the
balloon also empties (i.e., deflates) and gradually resumes its
former shape, once again becoming flush with the external wall of
the microcatheter. Inflating fluid can be removed by suction. With
deflation, the occlusion is gradually removed and the blood flow
gradually restored.
[0283] If reperfusion is sufficient but postconditioning has
already been performed on a previous pass, the microcatheter and
pushwire are removed from the body in step 2111. In a given pass,
after unsheathing the clot-capturing reperfusion member in step
2106 the operator should allow the clot-capturing reperfusion
member to expand into the clot until wait time t has elapsed. To
simultaneously remove the microcatheter and pushwire, an operator
may hold the proximal ends of the pushwire and microcatheter
together and translate them proximally until they are completely
withdrawn from the body in accordance with some embodiments. The
clot-capturing reperfusion member is not resheathed in the
microcatheter during its exit from the body, but instead passes,
along with the microcatheter and pushwire, within and through the
intermediate catheter (if present) and/or the larger catheter.
Therefore, the intermediate and/or larger catheters remain in place
while the microcatheter and pushwire are removed from the body.
Optionally, suction may be applied through the larger catheter
and/or intermediate catheter to limit the dispersion of secondary
emboli.
[0284] In step 2112, an operator determines whether clot material
has been sufficiently removed by the clot-capturing reperfusion
member. The status of reperfusion may inform this inquiry. Thus, in
some embodiments, the status of reperfusion is assessed by, for
example, injecting a contrast agent through the large catheter and
performing angiography to view the diffusion of the contrast agent.
In some embodiments, the reperfusion member itself is inspected
(e.g., visually) to determine whether the degree of retrieved clot
material is sufficient. Sufficiency may depend on numerous factors
including, but not limited to, changes in perfusion.
[0285] Following step 2112, if a sufficient amount of clot material
has been retrieved, as evidenced in some embodiments by the status
of reperfusion, the procedure is completed and any remaining
catheters are removed from the body according to step 2113.
However, if none or an insufficient amount of clot material has
been retrieved, and if a predetermined maximum number of passes has
not yet been completed, a new pass is initiated in step 2109 with
the insertion of a new guidewire.
Intermediate Double-Lumen Balloon Catheters
[0286] FIGS. 22A and 22B illustrate an additional way of using a
balloon for postconditioning is to use an additional catheter 2202
disposed between the microcatheter 102 and the large catheter (e.g.
size 6 French guide catheter) 2204. This additional catheter 2202
may be a double lumen balloon catheter (herein referred to as
"intermediate double lumen catheter"), and may be of size 5 French.
The intermediate double lumen catheter may be any number of sizes,
but is likely to range from 3 French to 5.5 French. The
intermediate double lumen catheter depicted in FIGS. 22A and 22B
bears balloon 2200. The balloon is attached to the intermediate
catheter in the attachment region 2230 on either side of the
inflating membrane and is delineated by radiopaque markers 2224.
However, intermediate single lumen catheters, which may or may not
have a balloon, may also be used. Flexibility is an important
characteristic for this intermediate double lumen catheter, to
allow it to pass through the torturous curves of cerebral vessels.
Reperfusion would be performed in cycles by using an inflating
solution. It would be controlled by a syringe or pump, similarly to
the balloon described in other sections of this document.
[0287] The large catheter 2204 is able to advance up to the
internal carotid artery at the distal portion of the neck. The
intermediate double lumen catheter 2202 would enter smaller
tortuous arteries, such as the MCA, to conduct postconditioning as
close to the location of the clot as possible, using a balloon 2200
near the distal end of the intermediate catheter.
[0288] The microcatheter 102 would be within the intermediate
double lumen catheter 2202 and deploy the pushwire 106 and
reperfusion member 108. The profile of the inner lumen 2206 will be
constant i.e. constant inner diameter. Here, the inflating solution
500 would have its own dedicated lumen 2208 within the walls 2210
and 2212 of the intermediate double lumen catheter. The inflating
solution would not come into contact with the pushwire 106 or
reperfusion member 108.
[0289] In a preferred embodiment for an intermediate double lumen
catheter FIGS. 22A-22B, there are separate coaxial lumens (similar
to FIG. 20C). The lumen for the inflating solution 2208 (herein
referred to as "inflating lumen") in the embodiment shown is
narrower than the lumen for the microcatheter 2206. Connectors 2012
(described in more detail with respect to FIGS. 20C and 20E) may
attach the walls of the two lumens. In the embodiment depicted in
FIG. 22A, 22B the diameter of the inner lumen 2206 is 0.026'', the
inner wall 2210 and outer wall 2212 are 100 .mu.m thick, and the
gap between the two walls is 100 .mu.m. These dimensions are
examples and may vary.
[0290] The outer diameter of the outer wall 2212 is preferred to be
about 0.050'' but may vary, for example, from about 0.040'' to
0.070''. Inflating holes 2222 through the outer wall 2212 of the
intermediate double lumen catheter connect the lumen used for the
inflating solution 500 to the balloon 2200.
Methods of Using Intermediate Double-Lumen Balloon Catheters
[0291] FIGS. 23A and 23B are process flow charts for performing
postconditioning with mechanical thrombectomy (an example of one of
the various techniques for achieving reperfusion) in accordance
with some embodiments of the present invention. For example, the
steps in FIGS. 23A and 23B may be applied to assemblies with
double-lumen balloon intermediate catheter embodiments of a flow
modulation member.
[0292] In step 2301, a large catheter (e.g., a 6 French catheter)
is inserted and guided, for example, from the femoral artery to the
neck. In step 2302, a guidewire is inserted through the large
catheter and navigated so that its distal end is at a position
distal to the location of the clot, for example, in a cerebral
artery.
[0293] In step 2303, an intermediate catheter (e.g., a 5 French
catheter) is inserted over the guidewire and advanced so that its
distal end is at a position (e.g., the sphenoidal (M1) segment of
the middle cerebral artery) that is closer to the clot than the
distal end of the large catheter. In the event of subsequent
passes, an intermediate catheter saves time in navigating a new
guidewire from the distal end of the large catheter to a position
distal to the location of the clot.
[0294] In step 2304, a microcatheter is inserted over the guidewire
and advanced so that its distal end is at a position distal to the
clot. In step 2305, the guidewire is removed from the microcatheter
and replaced with a pushwire. The pushwire has a reperfusion member
coupled to its distal end. Some reperfusion members (such as those
that may have clot-capture functionality) may have a self-expanding
region adapted for engaging with a clot (i.e., an "active region").
If using a clot-capturing reperfusion member, the active region of
the reperfusion member may be advanced within the microcatheter so
as to be adjacent to the clot. Thus, when the microcatheter is
retracted proximally to unsheathe the reperfusion member, as in
step 2306, the active region will expand and engage with the clot.
During all passes with a clot-capturing reperfusion member, the
microcatheter should be sufficiently retracted so that the
reperfusion member contacts the clot.
[0295] Following step 2306, the status of reperfusion should be
assessed and the elapsed time tracked. The reperfusion status may
be assessed by, for example, injecting a contrast agent (e.g., a
bolus of radiopaque solution) through the large catheter and
performing angiography to view the diffusion of the contrast agent.
Suitable contrast agents may include, but are not limited to,
iothalamate meglumine, diatrizoate meglumine, and other
iodine-containing solutions. If the artery is not reperfused, then
proceed to step 2307 in order to wait and check reperfusion status
again. If reperfusion has occurred then proceed with either (1)
postconditioning 2310, if postconditioning has not been already
performed on a prior pass; or (2) step 2311, which consists of
extracting the microcatheter and pushwire from the body, if
postconditioning was performed previously.
[0296] Postconditioning cycles are performed by inflating and
deflating the balloon (via the dedicated lumen of the intermediate
catheter) to occlude and reperfused the artery, respectively. The
inflation/deflation may be performed manually (e.g. with a syringe)
and automatically (e.g. with a pump and computerized control
system). Beneficial agents may be delivered during postconditioning
or other times through lumens that lead to the artery.
[0297] In step 2306, if the blood vessel has not been sufficiently
reperfused, then proceed to step 2307 where inflating fluid is
pumped into the inflating lumen of the intermediate double-lumen
catheter, thus inflating the flow modulation member and occluding
the blood vessel. A determined period of wait-time "t" (e.g., about
5 minutes) is allowed so that the clot-capturing reperfusion member
may expand into and engage with the clot. After wait time t, the
flow modulation member is deflated and the status of reperfusion is
assessed again. If the blood vessel has not been adequately
reperfused, proceed with step 2308 where the microcatheter and
pushwire are removed. If a predetermined maximum number of passes
has not yet been completed, a new pass is initiated in step 2309
with the insertion of a new guidewire. Steps 2304-2309 are repeated
in subsequent passes until either (1) the blood vessel is
sufficiently reperfused, in which case proceed with either step
2310 if postconditioning has not been already performed or step
2311 if postconditioning performed previously, or (2) the
predetermined maximum number of passes has been completed, in which
case proceed with step 2313.
[0298] If the blood vessel is sufficiently reperfused after step
2306 or step 2307, postconditioning will be performed using the
flow modulation member unless postconditioning was performed on a
previous pass. If reperfusion is sufficient and postconditioning
has not been performed on a previous pass, the flow modulation
member (i.e., a balloon) is inflated and deflated in step 2310
according to a determined series of one or more postconditioning
cycles. In contrast to some other embodiments, the flow modulation
member can be inflated without the operator performing additional
functions to create a seal. Examples of postconditioning cycles are
described in greater detail elsewhere herein.
[0299] According to some embodiments of the present invention, the
balloon is inserted with, attached to, and flush with the external
wall of the microcatheter. The balloon may be inflated and deflated
either by manual or by automatic pumping of inflating fluid in and
out of the inflation lumen of the double-lumen intermediate
catheter, which is continuous with the balloon lumen via inflation
holes. When inflating fluid is pumped through the inflation lumen
of the double-lumen intermediate catheter, it flows through the
inflation holes into the balloon. The balloon membrane expands
against the blood vessel, blocking a substantial portion of the
vessel's lumen. In a preferred embodiment, the balloon membrane
contacts the inner lumen of the blood vessel to create a complete
occlusion of blood flow. The balloon membrane is flexible so that
it will conform to the blood vessel's walls. By having a blood
flow-occluding balloon in place, a stable hemodynamic environment
is created, which helps minimize the risk of distal embolization.
In some embodiments, this increases the benefits of
postconditioning by controlling when reperfusion first occurs, so
that postconditioning may be performed from the onset of
reperfusion.
[0300] Upon removal of inflating fluid from the inflation lumen of
the double-lumen intermediate catheter, the balloon also empties
(i.e., deflates) and gradually resumes its former shape, once again
becoming flush with the external wall of the microcatheter.
Inflating fluid can be removed using suction. With deflation, the
occlusion is gradually removed and the blood flow gradually
restored.
[0301] If reperfusion is sufficient but postconditioning has
already been performed on a previous pass, the microcatheter and
pushwire are removed from the body in step 2311. In a given pass,
after unsheathing the clot-capturing reperfusion member in step
2306 the operator should allow the clot-capturing reperfusion
member to expand into the clot until wait time t has elapsed. To
simultaneously remove the microcatheter and pushwire, an operator
may hold the proximal ends of the pushwire and microcatheter
together and translate them proximally until they are completely
withdrawn from the body in accordance with some embodiments. The
clot-capturing reperfusion member is not resheathed in the
microcatheter during its exit from the body, but instead passes,
along with the microcatheter and pushwire, within and through the
double-lumen intermediate catheter and the larger catheter.
Therefore, the double-lumen intermediate catheter and/or larger
catheters remain in place while the microcatheter and pushwire are
removed from the body. Optionally, suction may be applied through
the larger catheter and/or double-lumen intermediate catheter to
limit the dispersion of secondary emboli.
[0302] In step 2312, an operator determines whether clot material
has been sufficiently removed by the clot-capturing reperfusion
member. The status of reperfusion may inform this inquiry. Thus, in
some embodiments, the status of reperfusion is assessed by, for
example, injecting a contrast agent through the large catheter and
performing angiography to view the diffusion of the contrast agent.
In some embodiments, the reperfusion member itself is inspected
(e.g., visually) to determine whether the degree of retrieved clot
material is sufficient. Sufficiency may depend on numerous factors
including, but not limited to, changes in perfusion.
[0303] Following step 2312, if a sufficient amount of clot material
has been retrieved, as evidenced in some embodiments by the status
of reperfusion, the procedure is completed and any remaining
catheters are removed from the body according to step 2313.
However, if none or an insufficient amount of clot material has
been retrieved, and if a predetermined maximum number of passes has
not yet been completed, a new pass is initiated in step 2309 with
the insertion of a new guidewire.
Other Multiple-Lumen Balloon Catheter Embodiments of a Flow
Modulation Member
[0304] In some balloon flow modulation systems, a conduit for
balloon-inflating fluid (e.g. a saline solution) or gas is attached
to the expandable balloon, and may be threaded through or alongside
the microcatheter or incorporated into the walls of the
microcatheter itself. According to some embodiments, a thinner and
more flexible tube for the inflating-fluid runs along the outside
of the microcatheter. The tube may run alongside the microcatheter
according to a helical, straight, or other pattern, and the tube
may either be unattached or attached (loosely, strongly, or just at
points) to the microcatheter. FIG. 24 illustrates a balloon 2400
fed by an inflating-fluid tube 2404, which is wrapped around the
outside of a microcatheter 2402 in a helical pattern.
[0305] According to some embodiments, a conduit for the
inflating-fluid is created as a hollow space within the walls of
the microcatheter. The conduit may run inside the microcatheter
walls according to a helical, straight, or other pattern. In
preferred embodiments, a helical pattern--winding around the
central longitudinal axis (identified in some illustrations by
reference numeral 902) of the microcatheter--is used for the
conduit or any aspects that add to microcatheter rigidity (e.g.,
posts). FIG. 25 illustrates a microcatheter with a hollow space
2506 between its outer walls 2504 and its inner walls 2502, held
open for the passage of inflating fluid by posts 2510. Posts may be
of different widths. In certain embodiments, the posts are so wide
that they connect to each other, and one continuous tubular or
rectangular conduit winds between the inner and outer walls of the
microcatheter in a helical pattern.
[0306] According to some embodiments, a separate microcatheter may
carry the inflating fluid through its central lumen (without a
guidewire inside). In these embodiments, the flow modulation
balloon may be located anywhere in the blood vessel and may not be
attached to the same microcatheter and guidewire that deliver a
reperfusion member.
[0307] The flow modulation member may be positioned in various
locations relative to the microcatheter, guidewire, clot, and
reperfusion member. According to some embodiments, a balloon may be
deployed (i.e., inflated) from or attached to a point proximal to
the distal end of the microcatheter, the distal end of the
microcatheter, on the guidewire proximal to the reperfusion member,
the distal end of the reperfusion member, or the distal end of the
guidewire. Unlike other embodiments of the flow modulation member,
a balloon does not need to be re-sheathed, just deflated. Because
the distal end of the microcatheter is not needed for re-sheathing,
the flow modulation balloon may be deployed either proximally or
distally to the clot. If the balloon is positioned on an extension
of the reperfusion member or the guidewire, distal to the clot, the
balloon could also prevent the clot or emboli from being left
behind or traveling to another vascular site when a reperfusion
member is pulled out of the body.
Methods of Using Other Multiple-Lumen Balloon Catheter Embodiments
of a Flow Modulation Member
[0308] FIGS. 26A and 26B are process flow charts for performing
postconditioning with mechanical thrombectomy (an example of one of
the various techniques for achieving reperfusion) in accordance
with some embodiments of the present invention. For example, the
steps in FIGS. 26A and 26B may be applied to assemblies with other
multiple-lumen balloon catheter embodiments of a flow modulation
member.
[0309] In step 2601, a large catheter (e.g., a 6 French catheter)
is inserted and guided, for example, from the femoral artery to the
neck. In step 2602, a guidewire is inserted through the large
catheter and navigated so that its distal end is at a position
distal to the location of the clot, for example, in a cerebral
artery.
[0310] In optional step 2603, an intermediate catheter (e.g., a 5
French catheter) is inserted over the guidewire and advanced so
that its distal end is at a position (e.g., the sphenoidal (M1)
segment of the middle cerebral artery) that is closer to the clot
than the distal end of the large catheter. In the event of
subsequent passes, an intermediate catheter saves time in
navigating a new guidewire from the distal end of the large
catheter to a position distal to the location of the clot.
[0311] In step 2604, a microcatheter is inserted over the guidewire
and advanced so that its distal end is at a position distal to the
clot. In step 2605, the guidewire is removed from the microcatheter
and replaced with a pushwire. The pushwire has a reperfusion member
coupled to its distal end. Some reperfusion members (such as those
that may have clot-capture functionality) may have a self-expanding
region adapted for engaging with a clot (i.e., an "active region").
If using a clot-capturing reperfusion member, the active region of
the reperfusion member may be advanced within the microcatheter so
as to be adjacent to the clot. Thus, when the microcatheter is
retracted proximally to unsheathe the reperfusion member, as in
step 2606, the active region will expand and engage with the clot.
During all passes with a clot-capturing reperfusion member, the
microcatheter should be sufficiently retracted so that the
reperfusion member contacts the clot.
[0312] Following step 2606, the status of reperfusion should be
assessed and the elapsed time tracked. The reperfusion status may
be assessed by, for example, injecting a contrast agent (e.g., a
bolus of radiopaque solution) through the large catheter and
performing angiography to view the diffusion of the contrast agent.
Suitable contrast agents may include, but are not limited to,
iothalamate meglumine, diatrizoate meglumine, and other
iodine-containing solutions. If the artery is not reperfused, then
proceed to step 2607 in order to wait and check reperfusion status
again. If reperfusion has occurred then proceed with either (1)
postconditioning 2610, if postconditioning has not been already
performed on a prior pass; or (2) step 2611, which consists of
extracting the microcatheter and pushwire from the body, if
postconditioning was performed previously. Postconditioning cycles
are performed by inflating and deflating the balloon (via the
inflation lumen of the catheter) to occlude and reperfused the
artery, respectively. The inflation/deflation may be performed
manually (e.g. with a syringe) and automatically (e.g. with a pump
and computerized control system). Beneficial agents may be
delivered during postconditioning or other times through lumens
that lead to the artery.
[0313] In step 2606, if the blood vessel has not been sufficiently
reperfused, then proceed to step 2607 where inflating fluid is
pumped into the single microcatheter lumen, thus inflating the flow
modulation member and occluding the blood vessel. A determined
period of wait-time "t" (e.g., about 5 minutes) is allowed so that
the clot-capturing reperfusion member may expand into and engage
with the clot. After wait time t, the flow modulation member is
deflated and the status of reperfusion is assessed again. If the
blood vessel has not been adequately reperfused, proceed with step
2608 where the microcatheter and pushwire are removed. If a
predetermined maximum number of passes has not yet been completed,
a new pass is initiated in step 2609 with the insertion of a new
guidewire. Steps 2604-2609 are repeated in subsequent passes until
either (1) the blood vessel is sufficiently reperfused, in which
case proceed with either step 2610 if postconditioning has not been
already performed or step 2611 if postconditioning performed
previously, or (2) the predetermined maximum number of passes has
been completed, in which case proceed with step 2613.
[0314] If the blood vessel is sufficiently reperfused after step
2606 or step 2607, postconditioning will be performed using the
flow modulation member unless postconditioning was performed on a
previous pass. If reperfusion is sufficient and postconditioning
has not been performed on a previous pass, the flow modulation
member (i.e., a balloon) is inflated and deflated in step 2610
according to a determined series of one or more postconditioning
cycles. In contrast to some other embodiments, the flow modulation
member can be inflated without the operator performing additional
functions to create a seal. Examples of postconditioning cycles are
described in greater detail elsewhere herein.
[0315] According to some embodiments of the present invention, the
balloon is inserted with, attached to, and flush with the external
wall of the catheter. The balloon may be inflated and deflated
either by manual or by automatic pumping of inflating fluid in and
out of the inflation lumen of the catheter, which is continuous
with the balloon lumen via inflation holes. When inflating fluid is
pumped through the inflation lumen of the catheter, it flows
through the inflation holes and into the balloon. The balloon
membrane expands against the blood vessel, blocking a substantial
portion of the vessel's lumen. In a preferred embodiment, the
balloon membrane contacts the inner lumen of the blood vessel to
create a complete occlusion of blood flow. The balloon membrane is
flexible so that it will conform to the blood vessel's walls. By
having a blood flow-occluding balloon in place, a stable
hemodynamic environment is created, which helps minimize the risk
of distal embolization. In some embodiments, this increases the
benefits of postconditioning by controlling when reperfusion first
occurs, so that postconditioning may be performed from the onset of
reperfusion.
[0316] Upon removal of inflating fluid from the inflation lumen of
the catheter, the balloon empties (i.e., deflates) and gradually
resumes its former shape, once again becoming flush with the
external wall of the catheter. Inflating fluid can be removed using
suction. With deflation, the occlusion is gradually removed and the
blood flow gradually restored.
[0317] If reperfusion is sufficient but postconditioning has
already been performed on a previous pass, the microcatheter
(whether it has single or multiple lumina) and pushwire are removed
from the body in step 2611. In a given pass, after unsheathing the
clot-capturing reperfusion member in step 2606 the operator should
allow the clot-capturing reperfusion member to expand into the clot
until wait time t has elapsed. To simultaneously remove the
microcatheter and pushwire, an operator may hold the proximal ends
of the pushwire and microcatheter together and translate them
proximally until they are completely withdrawn from the body in
accordance with some embodiments. The clot-capturing reperfusion
member is not resheathed in the microcatheter during its exit from
the body, but instead passes, along with the microcatheter and
pushwire, within and through the intermediate catheter (if present)
and/or the larger catheter. Therefore, the intermediate and/or
larger catheters remain in place while the microcatheter and
pushwire are removed from the body. Optionally, suction may be
applied through the larger catheter and/or intermediate catheter to
limit the dispersion of secondary emboli.
[0318] In step 2612, an operator determines whether clot material
has been sufficiently removed by the clot-capturing reperfusion
member. The status of reperfusion may inform this inquiry. Thus, in
some embodiments, the status of reperfusion is assessed by, for
example, injecting a contrast agent through the large catheter and
performing angiography to view the diffusion of the contrast agent.
In some embodiments, the reperfusion member itself is inspected
(e.g., visually) to determine whether the degree of retrieved clot
material is sufficient. Sufficiency may depend on numerous factors
including, but not limited to, changes in perfusion.
[0319] Following step 2612, if a sufficient amount of clot material
has been retrieved, as evidenced in some embodiments by the status
of reperfusion, the procedure is completed and any remaining
catheters are removed from the body according to step 2613.
However, if none or an insufficient amount of clot material has
been retrieved, and if a predetermined maximum number of passes has
not yet been completed, a new pass is initiated in step 2609 with
the insertion of a new guidewire.
Catheter-Constrained Embodiments of a Flow Modulation Member
[0320] The flow modulation member may be self-expanding and
attached to the pushwire proximal to the reperfusion member. In
these embodiments, the flow modulation member is deployed by
translating the microcatheter so as to unsheathe the flow
modulation member. To create cycles, flow is restored by
resheathing the flow modulation member with the microcatheter.
[0321] According to some embodiments, the flow modulation member
features an umbrella-like shape. FIGS. 27A-27C illustrates an
embodiment of an umbrella-like flow modulation member 2700 in a
fully expanded state with views from three different angles. The
microcatheter 2706 has been translated proximally along the
pushwire 2708 to release the flow modulation member 2700. The
proximal portion of the flow modulation member 2700 exits the
distal end of the microcatheter 2706 while the distal portion of
the flow modulation member 2700 contacts the luminal walls 114 of
the blood vessel to occlude blood flow from the proximal direction
116. The flow modulation member 2700 has struts 2704 to support a
blood-flow-occluding membrane 2702. A simplified version of a
reperfusion member 108 is attached to the pushwire 2708 distal to
the flow modulation member 2700 at joint 110.
[0322] In the embodiment shown in FIGS. 27A-27C, the flow
modulation member 2700 is designed with a strut length of about 1.4
mm for blood vessels with a radius of 1 mm, and is positioned with
the location of its proximal strut ends about 10 mm proximal to the
base of the reperfusion member. Generally, the distance between the
location of a flow modulation member's proximal strut ends and the
base of a reperfusion member may range anywhere from several
centimeters to none (e.g., overlapping).
Frames and Struts
[0323] In accordance with certain embodiments, one or more struts
form the frame of the flow modulation member. In an umbrella-like
flow modulation member, struts generally exert a force to expand
latitudinally and may spread the occlusion membrane across the
blood vessel aperture. Structures, geometries, patterns, and
numbers of struts in a flow modulation member may be varied to
achieve a desired force of expansion, flexibility, and ease of
re-sheathing. To optimize the opening and closing trajectory, force
against the blood vessel wall, resistance against blood flow, and
degree of occlusion, the flow modulation member may have a
different number of primary struts, secondary struts, and
non-linear geometries. FIG. 28 illustrates an embodiment of an
umbrella-like flow modulation member expanded latitudinally from
the central longitudinal axis 902 with an occlusion membrane 2802
supported by a lattice pattern of struts 2800. While the lattice
has advantages, if the density of lattice pattern of struts 2800 is
too high the ease of re-sheathing the flow modulation member may be
hindered.
[0324] According to a preferred embodiment, FIGS. 29 and 30
illustrate two views of an umbrella-like flow modulation member
2906 with six primary longitudinal struts 2908. Although six
primary struts are preferred, a smaller or larger number of primary
struts may be used. In FIG. 29, the primary struts 2908 span the
substantial length of the flow modulation member 2906, attaching at
their proximal ends to a pushwire 2912 at connection 2904 to ring
2902, and running parallel to a plane of the central longitudinal
axis 902 while expanding latitudinally. However, the edge 2900 of
an occlusion membrane may extend past the distal ends of the
primary struts 2908. As shown in FIGS. 29 and 30, the outer circle
(shown in dotted lines in FIG. 29) is the distal edge of the
occlusion membrane 2900.
[0325] In accordance with some embodiments, the form and curvature
of the self-expanding primary struts must be sufficient to reach
the targeted blood vessel wall with sufficient spring force to
block blood flow when unsheathed from the microcatheter. FIGS.
31A-31D illustrate four exemplary embodiments of primary strut
curvature when the strut is in its natural expanded state from a
view parallel to the central longitudinal axis. For each
embodiment, a strut 2908 is shown between the central longitudinal
axis 902 where it connects to pushwire 2708 and contacts the blood
vessel wall 114 (also shown in previous illustrations).
[0326] In the preferred embodiment of FIG. 31A, a first section
3100 of the strut 2908(a) curves with increasing slope away from
the central axis 902, convex to the flow of blood. A second section
3102 of the strut 2908(a) is substantially straight and extends
from the first curved section 3100. A third section 3104 of the
strut 2908(a) continues from the second section 3102, concave to
the flow of blood with decreasing slope relative to the central
axis 902. A fourth section 3106 of the strut 2908(a) is
substantially parallel to the central axis 902 and extends the
third section 3104 until the strut is flush with the blood vessel
wall 114. The fourth section 3106 increases the area of contact
between the strut and the blood vessel wall, which further
stabilizes the flow modulation member, thus strengthening its
blood-flow-blocking capabilities by increasing the amount of force
it can apply without damaging the blood vessel and surrounding
brain tissue. Thus, the fourth section 3106 may allow an operator
to perform postconditioning with greater speed and
effectiveness.
[0327] Another advantage of the primary strut curvature shown in
FIG. 31A is that the small slope of the first section 3100
(relative to the central longitudinal axis 902) provides finer
control of the aperture of the flow modulation member because
movement of the umbrella-like flow modulation member in and out of
the microcatheter along the first section 3100 of the struts
translates into a smaller difference in the area of the luminal
latitudinal plane blocked by the member than if the same movement
is made along the second section 3102.
[0328] Other primary strut curvatures are contemplated. Generally,
a convex umbrella surface is more stable than a concave umbrella
surface because blood flow pushing against a concave configuration
has a greater propensity to collapse the umbrella. Embodiments of a
flow modulation member with convex umbrella surfaces tend to exert
more radial force against the blood vessel wall as blood flows
against them, therefore creating a tighter seal. For example, FIG.
31B illustrates a strut 2908(b) with one curved section of
continuously increasing slope away from the central axis 902,
convex to the flow of blood for greater stability. Meanwhile, FIG.
31C illustrates a strut 2908(c) with one curved section of
continuously decreasing slope away from the central axis 902,
concave to the flow of blood, useful perhaps for milder occlusions
or other clinical indications. FIG. 31D illustrates a strut 2908(d)
with two curved sections, the proximal section continuously
increasing in slope and convex to the flow of blood, the second
distal section continuously decreasing in slope and concave to the
flow of blood.
[0329] In accordance with most embodiments, the potential radius of
an umbrella-like flow modulation member at its distal end, should
be substantially similar to, or greater than, the radius of the
targeted blood vessel. When fully deployed, the distal end of the
flow modulation member is compressed by the blood vessel walls.
This compression allows the flow modulation member to exert an
outward radial force on the vessel walls. Thus, different sizes of
flow modulation members are necessary to achieve the desired
outward radial force for different sizes of blood vessels. For
example, the flow modulation member's distal radius may range from
1 mm to 4 mm in its deployed state.
[0330] FIGS. 32A-32B illustrate the angle between the central
longitudinal axis 902, which is parallel to pushwire 2708, and a
line 3204, or 3206 respectively, from the proximal junction to the
distal end of a primary strut of a flow modulation member in,
respectively, working state and resting state. The change in the
angle results a residual outward radial force on the blood vessel
walls 114. As illustrated in FIG. 32A, during working state, when
the umbrella of the flow modulation member is constrained by blood
vessel walls 114 at distal radius 3210, this angle is referred to
as the working angle 3200. As illustrated in FIG. 32B, during
resting state, when the umbrella of the flow modulation member is
deployed but not constrained by blood vessel walls 114 at distal
radius 3212, this angle is referred to as the set angle 3202. In
most embodiments, the set angle is greater than the working angle.
For example, the set angle 3202 in FIG. 32B may be 60 degrees,
while the working angle 3200 in FIG. 32A may be 45 degrees. The
appropriate umbrella length for a given blood vessel radius may be
calculated from the set and working angles. Thus, the working angle
3200 and set angle 3202 may be used to determine the appropriate
longitudinal extension in the working state 3208 and resting state
3214 of the umbrella along the central axis 902.
[0331] The extent of the latitudinal expansion of a flow modulation
member for a given translation of a microcatheter is another
consideration when determining the slope(s) and/or length(s) of the
primary struts. In certain embodiments, a rapid expansion of an
umbrella-like flow modulation member with minimal translation of
the microcatheter may be desirable. In other embodiments, a more
gradual expansion may afford greater control. The optimal rate of
flow modulation member deployment, such as umbrella expansion, per
pushwire translation may be varied depending on the procedure and
status of the clot.
[0332] According to some embodiments, the resistance of a flow
modulation member against blood flow and its outward radial force
against the blood vessel wall varies at different points of its
profile.
[0333] In some embodiments, a flow modulation member is designed so
that the radial force changes over the course of the member's
deployment, to minimize friction between the member and the blood
vessel wall. For example, in certain embodiments, the radial force
of an umbrella-like flow modulation member may decrease as the
radius of the partially deployed umbrella approaches that of the
blood vessel. In alternative embodiments, a fully expanded flow
modulation member may not completely contact the blood vessel wall.
According to some embodiments, an operator may choose not to deploy
the flow modulation member to its full extent. In cases where a
flow modulation member does not contact or loosely contacts the
blood vessel wall, only partial occlusion may be achieved and some
blood may flow around the member.
[0334] In accordance with certain embodiments, the cross-sections
of the self-expanding struts may take various shapes and dimensions
in order to reach the targeted blood vessel wall with sufficient
spring force to block blood flow. FIGS. 33A-33E illustrate five
exemplary embodiments of primary strut cross-sections, including
the depth 3300 and the width 3302. The depth 3300 of a strut is
substantially parallel to a radial line 3304 from the central
longitudinal axis 902 (along which the pushwire 2708 travels) to
the blood vessel wall 114.
[0335] In the preferred embodiment of FIG. 33A, a rectangular
cross-section of a strut is shown with a greater width 3302 (about
70 .mu.m) than depth 3300 (about 50 .mu.m), in order to increase
the strut's ability to support an occlusion membrane. However, a
greater depth 3300 may increase the ability of the struts to exert
radial force. Therefore, a greater depth may be desired, as shown
in FIG. 33B, where a rectangular cross-section of a strut is shown
with a greater depth 3300 (about 70 .mu.m) than width 3302 (about
50 .mu.m). The square cross-section of a strut shown in FIG. 24C,
with depth 3300 (about 70 .mu.m) and width 3302 (about 70 .mu.m),
may be selected for both support and greater radial force.
Generally, a square or rectangular cross-sectional shape may be
easier to manufacture if cutting a strut from sheets, cones, or
cylinders. Additionally, a square or rectangular cross-sectional
shape may eliminate the need for electro-polishing to smooth the
edges of a strut.
[0336] Other strut cross-sectional shapes are contemplated. For
example, FIG. 33D illustrates a strut with an oval cross-section,
having a greatest depth 3300 (about 50 .mu.m) and greatest width
3302 (about 70 .mu.m). Meanwhile, FIG. 33E illustrates a strut with
a circular cross-section, having constant diameter (about 70
.mu.m). In some embodiments of an umbrella-like flow modulation
member, the shape and dimensions of a strut cross-section may even
change across the length of the strut to achieve varying pressures
and other characteristics at different points of the umbrella.
[0337] In accordance with preferred embodiments, the struts are
made from nitinol. However, other shape-memory materials,
shape-memory alloys, or super-elastic materials that exert pressure
to expand to their set shape may be used. Such materials include,
for example, nickel titanium alloy, stainless steel, or cobalt
chromium alloys.
[0338] Different manufacturing methods may be used for the
different types of struts. Struts may be formed out of a single
piece of material or made from different pieces and assembled
together. A single piece of material is preferred, when readily
manufacturable, because it simplifies the attachment process and
may afford greater structural integrity. Laser cutting may be used
to manufacture the struts. For example, the struts may be cut from
a cone that has an envelope similar to the desired expanded shape
of an umbrella-like flow modulation member and a thickness as close
as possible to the depth desired for the strut cross sections.
Alternatively, the struts may be cut from a flat sheet of material
or from a sheet of material that has been bent to the desired
curvature of the struts. A substantially flat sheet of material
will generally result in struts with rectangular cross
sections.
[0339] Electro-polishing may or may not be needed, but may be used,
in combination with the other methods described, to round the edges
of individual struts to achieve oval or circular cross sections
like those shown in FIGS. 33D and 33E respectively. In other
embodiments, struts with oval or circular cross sections may be
achieved by using thin wires. Likewise, bending and heat setting
may or may not be used, in combination with the other methods
described, to form and perfect the curvature of the struts.
[0340] In some embodiments, the primary struts of an umbrella-like
flow modulation member may be cut from a single piece of material.
The embodiment shown in FIG. 34A illustrates how this continuous
piece has a ring-base 3402 at its proximal end. This ring-base 3402
is placed over and attached to the pushwire 2708. According to some
embodiments, a ring-base 3402 is attached to the pushwire via
thermal interference fitting. To use thermal interference fitting,
the ring-base is made initially with a diameter too small to fit
over the pushwire. When heated, the ring-base expands so it can be
placed over the pushwire. As it cools, the ring-base tightens
around the pushwire to create a firm attachment. Alternatively, the
pushwire may be cooled to a low temperature such that the
pushwire's diameter decreases. In this case, the ring-base would be
manufactured at its final diameter. The ring-base is placed onto
the cooled pushwire. As the pushwire expands to its normal diameter
(at room temperature), it creates a firm attachment with the
ring-base.
[0341] If the primary struts are made from separate parts, as shown
in FIG. 34B-34D, the proximal ends of the struts 3404 must be
securely attached to the pushwire 2708. The struts 3404 may be
attached in any number of ways including but not limited to:
welding the struts directly to the pushwire, soldering the struts
directly to the pushwire (using, for example, platinum solder), or
attaching the struts to a metal or plastic ring, which is either
first or subsequently attached to the pushwire. The embodiment
shown in FIG. 34C illustrates how the struts 3404 are attached to
the pushwire 2708 with solder 3406.
[0342] In further embodiments, a sleeve or a low-profile ring may
be placed on top of the various attachment junctions to promote
smooth deployment and retrieval and to relieve strain on the
attachments. FIG. 34D illustrates how a sleeve 3408 may be attached
to the pushwire 2708 with solder 3406 to cover the proximal ends of
struts 3404. A sleeve may be made of a heat-shrinkable material
such as polyethylene terephthalate, nylon, or another polymer or
elastic material. Adhesive, molding, press-fitting, interference
fitting, curing, epoxy, or other attachment methods or combinations
thereof may also be used to attach a sleeve.
[0343] As illustrated in FIGS. 35 and 36, according to some
embodiments, a flow modulation member may incorporate secondary
struts. The objectives of using secondary struts 3504 may include
increasing pressure against blood flow at desired areas of the
member, supporting a membrane of the member, and providing a closer
fit between the member and blood vessel walls. For example,
additional struts 3502 spaced between the secondary struts 3504 and
around the distal end of an umbrella-like flow modulation member
and/or additional struts 3504 around the mid-section of the member
may be effective. The outer circle 3502 of the embodiment in FIGS.
35, 36 may represent the distal edge of a membrane, a secondary
latitudinal strut, or both.
[0344] Distal secondary struts may advantageously facilitate
contact between the distal open end of an umbrella-like flow
modulation member and the luminal blood vessel wall by creating a
more perfectly circular shape, instead of straight edges 3700 (as
shown in FIG. 37) of membrane between the primary struts, thus
better conforming the distal end of the member to the latitudinal
plane of the vessel wall. This is illustrated, for example, in
FIGS. 37 and 38 by the distal rounded distal edge 3702, instead of
straight membrane edges 3700. In addition to more firmly engaging
the blood vessel wall, secondary struts may minimize trauma to the
blood vessel walls by improving the distribution of radial force. A
variety of structures and techniques for improving and minimizing
trauma are discussed above and below
[0345] Latitudinal struts may be added to the mid-section of an
umbrella-like flow modulation member in order to further stabilize
the member, make the mid-section of the umbrella more rigid, and/or
exert pressure at various points against blood flow. The
embodiments in FIGS. 35 and 36 also feature latitudinal struts 3604
(and potentially 3602) around the mid-section of the member.
[0346] The latitudinal struts need not be circular in
configurations. In some preferred embodiments, a latitudinal strut
is configured to include a series of straight sections and bends,
which may be referred to as a zigzag configuration. For example,
the embodiments in FIGS. 36, 38A and 38B feature a zigzag
configuration for a latitudinal strut 3802(a). 3802(b) and 3604 at
the distal end of an umbrella-like flow modulation member. In
addition to a zigzag-configured latitudinal strut 3802 at the
distal end of an umbrella-like flow modulation member, the
embodiment in FIG. 36 features a zigzag-configured latitudinal
strut 3602 around the mid-section of the member. The zigzag
configuration is useful because it exerts latitudinal force while,
as shown in FIG. 38B, folding up easily to contract back into the
microcatheter 2706. Configurations other than zigzag may also be
used for latitudinal struts. Of course, undulations and other wire
patters are also desirable in certain design configurations.
[0347] In some embodiments, secondary struts include additional
longitudinal struts that are not attached to the membrane of an
umbrella-like flow modulation member. These stabilizing
longitudinal struts may contact the blood vessel wall during
deployment in order to center and further support the member. In
certain embodiments, secondary struts include longitudinal struts
that may pass through the hollow center of an umbrella-like flow
modulation member, perhaps crossing the central axis 902.
[0348] According to some embodiments, secondary struts may be
formed using the same materials with the same processes as primary
struts. However, a secondary strut may have differently-shaped
cross-section (e.g., a near-round cross-section) with a smaller
diameter (e.g., about 50 .mu.m) than the primary struts. Secondary
struts may be attached to primary struts via methods including
welding, soldering, or adhesion. However, in preferred embodiments,
when efficient, the primary and secondary struts are cut from the
same piece of original material.
[0349] In some embodiments, radiopaque materials may be attached to
or used to make or coat a portion or all of the struts (or strut
attachments, e.g., solder) of a flow modulation member. The
radiopaque material or materials may include: platinum, cobalt,
molybdenum, silver, tungsten, iridium, polymers, or various
combinations. In preferred embodiments, three of the longitudinal
struts are made from or coated with a radiopaque material. The
marked struts may be equidistant from each other so that that state
of expansion can be accurately observed from many angles. In a
further preferred embodiment, a flow modulation member has platinum
radiopaque markers welded to the distal ends of the primary struts.
Alternatively, or in addition to marking the distal ends of the
struts of a flow modulation member, radiopaque material may be used
to mark the proximal ends of the struts, the pushwire at a point
close to the base of the struts, the pushwire at points adjacent to
where the open end of the flow modulation member touches when
re-sheathed, and the distal end of the microcatheter.
Membranes
[0350] In accordance with some embodiments, the struts of an
umbrella-like flow modulation member support a membrane, which
blocks or slows the flow of blood when deployed in a vessel. In
some embodiments, the membrane is flexible enough to allow the flow
modulation member to pass through the brain's narrow and tortuous
blood vessels. In preferred embodiments, the membrane is
impermeable to blood and is elastic. To achieve these
characteristics, the membrane of the umbrella may be constructed
from various materials. Polypropylene is preferred but other
materials may be used such as, thermoplastic polymers, elastomeric
silicones, latexes, other polymers or a blend thereof. An example
is ENGAGE.TM. polyolefin elastomers available from the Dow Chemical
Company (Midland, Mich.). Elasticity allows the membrane to expand
and contract with the movement of the struts. However, in other
embodiments, the membrane need not be elastic, instead simply
bending or folding with the movement of the struts. In some
embodiments, the membrane need not even be impermeable.
[0351] In additional to polymers, the membrane may be made from
other materials that block or slow blood flow, including types of
woven fabric mesh or a web of fabric (e.g., made from Dacron). The
membrane, as well as other or all parts of a flow modulation
member, may be coated with a non-stick substance to reduce friction
and enable easy movement through and upon exit from the
microcatheter. Suitable friction-reducing or lubricating substances
may include, but are not limited to, silicone-based lubricating
agents, and polytetrafluoroethylene or other polymer coatings.
[0352] According to some embodiments, various parts of the flow
modulation system may carry chemicals, pharmaceuticals, or other
agents. For example, an umbrella-shaped flow modulation member or a
reperfusion member may be coated with an agent. In a preferred
method, an agent is held within the hollow space inside the
umbrella, between the pushwire and the membrane.
[0353] According to preferred embodiments, the membrane material
near the distal outer edge of an umbrella-like flow modulation
member presents a rounded or even edge to the blood vessel wall. In
order to conform to the blood vessel wall, the distal edge of the
membrane may also be stiffer, thicker, and/or of a different
material than the rest of the membrane. In the embodiment shown in
FIG. 37, the distal edge 3702 of the membrane (identified at 3502
in FIG. 36) is both stiffer and thicker than the rest of the
membrane 2702 but still of the same material. This alteration to
the distal edge, which might otherwise consist of straight edges
stretched between primary struts, conforms the distal edge of the
membrane to the latitudinal plane of the blood vessel wall and thus
creates a tighter seal. This is illustrated, for example, in FIG.
37 by the curved shape of the distal membrane edge 3702, instead of
the straight membrane edges 3700. This form-asserting distal edge
may also reduce friction between the flow modulation member and the
blood vessel wall, limiting trauma to the blood vessel wall--that
is already weakened from the ischemia. In preferred embodiments,
and as shown in FIG. 39, the distal edge 3502 of the membrane 3900
extends past the distal ends of the struts 2908. In some
embodiments, and as shown in FIG. 40, areas of the membrane
proximal to the distal edge may be less rounded and instead
stretched into straight membrane planes 4002.
[0354] In most embodiments, a method is used to connect the
membrane to the primary struts that minimizes the possibility of
the membrane detaching from the struts during deployment of the
flow modulation member. Appropriate methods for attaching the
membrane include, but are not limited to adhesion, or encasement of
the struts either completely or partially.
[0355] In preferred embodiments, as shown in FIGS. 39, 40, 42A-42D
and 43 an umbrella-like flow modulation member has a membrane 3900
that completely encases the struts in the latitudinally expanding
regions of the member. Encasement may be accomplished, for example,
by melting and molding the plastic around the struts. This is
illustrated by section view 42C-42C in FIG. 42A, FIG. 42C, as well
as FIG. 43, where the struts 2704 are illustrated as embedded
within the membrane 3900. As illustrated in FIG. 29, if the struts
2908 and ring-base 2902 are one piece, and if a membrane encases
the struts 2908, then the proximal membrane edge may be near the
distal edge of the ring-base 2904. The view in FIG. 41E illustrates
the ridges created by the struts in the membrane 3900.
[0356] In another attachment solution FIG. 39, an attachment ring
3902 may be a separate piece and made of a material such as steel
or other metallic or non-metallic material. The attachment ring
3902 is compressed, using swaging, over the proximal ends of the
flow modulation member and the pushwire 2708. Swaging creates even
sealing without heating the nitinol, which would potentially alter
the flow modulation member's shape memory.
[0357] In alternative embodiments, a membrane may be attached to
the outside or inside of the struts of an umbrella-like flow
modulation member. The embodiment shown in FIG. 44 shows a membrane
2702 attached to the outside of the primary struts 2704. This
attachment of a membrane to the outside of the struts may be more
efficient from a manufacturing perspective; however, attaching a
membrane to the inside of the struts may reduce friction between
the membrane and the microcatheter.
[0358] In some embodiments, the membrane is tapered to be, for
example, thinner at its proximal end. In accordance with the
embodiments shown in FIGS. 39 and 44, the membrane 2702 may extend
toward the proximal end of the struts 2704 and into the attachment
ring 3902. The membrane may extend into a ring or a sleeve covering
the proximal base of the struts to create a good seal.
[0359] According to some embodiments illustrated in FIGS. 45A-45C,
the shape or configuration that the flow modulation member's struts
make when expanded may be different than an umbrella in appearance.
The flow modulation member may take any shape or configuration
capable of being deployed and retracted as well as capable of
allowing the membrane to modulate blood flow. For example, a flow
modulation member where the struts 4500 terminate together at the
distal end may be used. FIG. 45A illustrates an embodiment of a
flow modulation member with this shape attached to a pushwire 2708.
Such embodiments pre-establish the placement and centering of the
flow modulation system and allow an operator to verify that no
sharp edges are making contact with the blood vessel wall. In
addition, such embodiments have the advantage of increasing the
contact area of the member with the blood vessel wall for greater
stability, more easily ensuring a smooth curved contact area of the
member with the blood vessel wall, and potentially fortifying the
ability of the member to block blood flow. A membrane may cover the
entire flow modulation member or a portion--any or a combination of
the proximal portion, the distal portion, and the generally
cylindrical portion in between--of the flow modulation member
struts. In the embodiment shown in FIG. 45B, the membrane 4502
covers the proximal portion 4504 of flow modulation member. In the
embodiment shown in FIG. 45C, the membrane 4508 covers the entire
flow modulation member as represented by reference numeral
4506.
[0360] According to some embodiments, the flow modulation member
may be designed so that the distal portion is not covered by a
membrane and this uncovered distal portion is deployed before the
membrane-covered portion. By deploying the uncovered portion first,
an operator may secure the placement and trajectory of the flow
modulation member prior to the active occlusion of blood flow. This
allows the operator to deploy the membrane-covered portion more
rapidly, safely, and confidently. To achieve these different
effects across the membrane-covered and uncovered portions of a
flow modulation member, the central cylinder portion may use a more
pliable pattern than lattice, cellular, or other more rigid
patterns. Straight struts, for example, would more easily allow
part of the flow modulation member to be released while part
remained in the microcatheter. The uncovered portions of the flow
modulation member may remain expanded throughout postconditioning.
In accordance with certain embodiments, a flow modulation member,
particularly the primary struts, may be marked with radiopaque
material to distinguish the membrane-covered and uncovered portions
of the flow modulation member.
[0361] According to other embodiments, a flow modulation member may
take the general form of a neurovascular stent. Neurovascular
stents have a naturally cylindrical shape that is tangent to the
blood vessel wall. A flow blocking membrane could be attached to
cover all or part of a stent.
[0362] In further embodiments, the flow modulation member is part
of the same element as the reperfusion member. FIGS. 46A-46C shows
a series of hybrid clot capture and flow modulation member
embodiments. In the embodiment shown in FIG. 46B, a flow-blocking
membrane 4602 covers the proximal portion 4604 of a reperfusion
member. A hybrid clot capture and flow modulation member may be
less expensive and may be easier to retract back into the
microcatheter and out of the body than multiple separate members.
Besides reducing the number of moving parts, a hybrid clot capture
and flow modulation member may allow flow modulation closer to the
clot.
[0363] In order to accommodate the membrane, a hybrid clot capture
and flow modulation member may need to be longer than a typical
reperfusion member. FIG. 46C illustrates the distal clot contact
area 4606 with this increase in length 4608, which may be, for
example, 10 mm. According to most embodiments, the proximal end of
a hybrid clot capture and flow modulation member would need to be
positioned close enough to the microcatheter so that a minimal push
of the microcatheter could re-sheathe the flow-blocking membrane
during postconditioning. Additional modifications may be made to
allow a hybrid clot capture and flow modulation member to remain
partially deployed without significantly deforming the portion of
the member in contact with the clot. For example, as illustrated in
FIGS. 47A and 47B, an area of the cylindrical portion 4608 (show
schematically as reference numeral 4612) between the membrane 4604
and the contact area 4606 for the distal clot 4710 may be made more
structurally flexible or proximally tapered to dissipate the
deforming force of re-sheathing on the distal clot contact area
4606. FIGS. 47A and 47B illustrate the clot contact area
schematically.
Methods of Using Catheter-Constrained Embodiments of a Flow
Modulation Member
[0364] FIGS. 48A and 48B are process flow charts for performing
postconditioning with mechanical thrombectomy (an example of one of
the various techniques for achieving reperfusion) in accordance
with some embodiments of the present invention. For example, the
steps in FIG. 48 may be applied to assemblies with
catheter-constrained embodiments of a flow modulation member.
[0365] In step 4801, a large catheter (e.g., a 6 French catheter)
is inserted and guided, for example, from the femoral artery to the
neck. In step 4802, a guidewire is inserted through the large
catheter and navigated so that its distal end is at a position
distal to the location of the clot, for example, in a cerebral
artery.
[0366] In optional step 4803, an intermediate catheter (e.g., a 5
French catheter) is inserted over the guidewire and advanced so
that its distal end is at a position (e.g., the sphenoidal (M1)
segment of the middle cerebral artery) that is closer to the clot
than the distal end of the large catheter. In the event of
subsequent passes, an intermediate catheter saves time in
navigating a new guidewire from the distal end of the large
catheter to a position distal to the location of the clot.
[0367] In step 4804, a microcatheter is inserted over the guidewire
and advanced so that its distal end is at a position distal to the
clot. In step 4805, the guidewire is removed from the microcatheter
and replaced with a pushwire. The pushwire has a flow modulation
member and a reperfusion member coupled to the pushwire near the
pushwire's distal end. Some reperfusion members (such as those that
may have clot-capture functionality) may have a self-expanding
region adapted for engaging with a clot (i.e., an "active region").
If using a clot-capturing reperfusion member, the active region of
the reperfusion member may be advanced within the microcatheter so
as to be adjacent to the clot. Thus, when the microcatheter is
retracted proximally to unsheathe the reperfusion member, as in
step 4806, the active region will expand and engage with the clot.
Depending on the distance that the microcatheter is translated
proximally, the flow modulation member may either be deployed or
sheathed while the reperfusion member's active region continues to
contact the clot. During all passes with a clot-capturing
reperfusion member, the microcatheter should be sufficiently
retracted, at some point, so that the reperfusion member contacts
the clot.
[0368] Following step 4806, the status of reperfusion should be
assessed and the elapsed time tracked. The reperfusion status may
be assessed by, for example, injecting a contrast agent (e.g., a
bolus of radiopaque solution) through the large catheter and
performing angiography to view the diffusion of the contrast agent.
The flow modulation member must be at least partially sheathed for
some time to allow diffusion of the contrast agent. Suitable
contrast agents may include, but are not limited to, iothalamate
meglumine, diatrizoate meglumine, and other iodine-containing
solutions. If the artery is not reperfused, then proceed to step
4807 in order to wait and check reperfusion status again. If
reperfusion has occurred then proceed with either (1)
postconditioning 4810, if postconditioning has not been already
performed on a prior pass; or (2) step 4811, which consists of
extracting the microcatheter and pushwire from the body, if
postconditioning was performed previously. Postconditioning cycles,
of occlusion and reperfusion, are performed by translating the
microcatheter, while holding the pushwire in place, to release
(unsheathe) and constrain (resheathed) the flow modulation member
and thereby blocking and unblocking the artery to varying degrees,
respectively. The inflation/deflation may be performed either
manually (e.g. by translation of the microcatheter by the operator)
or automatically (e.g. with the translation of the microcatheter
and timing thereof made by a computerized control system).
Beneficial agents may be delivered during postconditioning or other
times through the intermediate catheter (if present), large
catheter, and microcatheter; however, these agents will only be
able to directly reach the infarct region at times when the flow
modulation member is not fully expanded against the blood vessel
wall.
[0369] In step 4806, if the blood vessel has not been sufficiently
reperfused, then proceed to step 4807 where the microcatheter is
alternatively translated proximally and distally while the
reperfusion member is held in place, in order to unsheathe and
re-sheathe the flow modulation member in cycles. A determined
period of wait-time "t" (e.g., about 5 minutes) is allowed so that
the clot-capturing reperfusion member may expand into and engage
with the clot. After wait time t, the flow modulation member is
deflated and the status of reperfusion is assessed again. If the
blood vessel has not been adequately reperfused, proceed with step
4808 where the microcatheter and pushwire are removed. If a
predetermined maximum number of passes has not yet been completed,
a new pass is initiated in step 4809 with the insertion of a new
guidewire. Steps 4804-4809 are repeated in subsequent passes until
either (1) the blood vessel is sufficiently reperfused, in which
case proceed with either step 4810 if postconditioning has not been
already performed or step 4811 if postconditioning performed
previously, or (2) the predetermined maximum number of passes has
been completed, in which case proceed with step 4813.
[0370] If the blood vessel is sufficiently reperfused after step
4806 or step 4807, postconditioning will be performed using the
flow modulation member unless postconditioning was performed on a
previous pass. If reperfusion is sufficient and postconditioning
has not been performed on a previous pass, the flow modulation
member is reversibly deployed in step 4810 according to a
determined series of one or more postconditioning cycles. Examples
of postconditioning cycles are described in greater detail
elsewhere herein.
[0371] By having a blood flow-occluding flow modulation member
unsheathed, a stable hemodynamic environment is created, which
helps minimize the risk of distal embolization. In some
embodiments, this increases the benefits of postconditioning by
controlling when reperfusion first occurs, so that postconditioning
may be performed from the onset of reperfusion.
[0372] If reperfusion is sufficient but postconditioning has
already been performed on a previous pass, the microcatheter and
pushwire are removed from the body in step 4811. In a given pass,
after unsheathing the clot-capturing reperfusion member in step
4806 the operator should allow the clot-capturing reperfusion
member to expand into the clot until wait time t has elapsed. To
simultaneously remove the microcatheter and pushwire, an operator
may hold the proximal ends of the pushwire and microcatheter
together and translate them proximally until they are completely
withdrawn from the body in accordance with some embodiments. The
clot-capturing reperfusion member is not resheathed in the
microcatheter during its exit from the body, but instead passes,
along with the microcatheter and pushwire, within and through the
intermediate catheter (if present) and/or the larger catheter.
Therefore, the intermediate and/or larger catheters remain in place
while the microcatheter and pushwire are removed from the body.
Optionally, suction may be applied through the larger catheter
and/or intermediate catheter to limit the dispersion of secondary
emboli.
[0373] In step 4812, an operator determines whether clot material
has been sufficiently removed by the clot-capturing reperfusion
member. The status of reperfusion may inform this inquiry. Thus, in
some embodiments, the status of reperfusion is assessed by, for
example, injecting a contrast agent through the large catheter and
performing angiography to view the diffusion of the contrast agent.
In some embodiments, the reperfusion member itself is inspected
(e.g., visually) to determine whether the degree of retrieved clot
material is sufficient. Sufficiency may depend on numerous factors
including, but not limited to, changes in perfusion.
[0374] Following step 4812, if a sufficient amount of clot material
has been retrieved, as evidenced in some embodiments by the status
of reperfusion, the procedure is completed and any remaining
catheters are removed from the body according to step 4813.
However, if none or an insufficient amount of clot material has
been retrieved, and if a predetermined maximum number of passes has
not yet been completed, a new pass is initiated in step 4809 with
the insertion of a new guidewire.
Primarily Electrically Controlled Flow Modulation Member
[0375] The degree of occlusion effectuated by the flow modulation
member may be directly controlled by electricity. One way to do
this is with an electro-active polymer ("EAP"). An example
embodiment using an EAP to control the postconditioning cycles of
the flow modulation member uses a configuration similar to the
umbrella flow modulation member described elsewhere herein, but
replaces the nitinol struts of the umbrella with struts made from
an EAP.
[0376] In an example embodiment illustrated in FIGS. 49A-49B,
includes sheets of EAP which are cut in bands of .about.750 .mu.m
wide and .about.2 mm long to form EAP struts 4908. The bands can be
a parallelepiped preferentially with rectangular faces although
other shapes are acceptable. The EAP struts may be encased in a
membrane 3900 (as illustrated). The struts are secured to the
pushwire 2708. The proximal ends of the struts are not encased in
the membrane. Instead, they are sandwiched between two electrode
rings 4904 and 4906. The two electrodes 4904 and 4906, the struts
4908 and the proximal part of the membrane 4912 are all securely
attached to the pushwire 2708 by a surrounding attachment ring
4902, fastened by a method such as crimping. Two opposite faces of
the EAP struts are illustrated perpendicular to a plane containing
the symmetry axis of the pushwire and the longest dimension. Each
face is connected to a wire 4940 and 4942 able to conduct
electricity running along the pushwire and can be connected to a
voltage source such as a battery, outside of the patient through
connectors.
[0377] The application of a voltage between the two faces of the
electroactive polymer causes the strut to bend in one direction.
Usually the cations contained in the polymer are able to migrate
(although this is not always the case), they are thus attracted
towards the face of the polymer that is negatively charged, causing
the polymer to bend. In this embodiment, we choose to connect the
voltage source such that the polymer will bend with its face with
the lower curvature--or greater radius of curvature--closer to the
pushwire 2708. In this configuration, three to eight struts are
distributed radially around the pushwire with their longest
dimension in the direction of the central axis 902, and all bending
away from the central axis when an appropriate voltage is applied.
The voltage necessary to induce the deformation of the
electroactive polymer struts is in the range of approximately
0.1-20V although a greater potential difference may be needed.
[0378] The struts create a scaffold for a membrane attached to
them. One way of attachment is encasing the struts within the
membrane, as depicted in FIGS. 49A and 49B. This membrane can be
made from a polymer such as latex, elastomers, PETE or fabric such
as Dacron.RTM.. The role of the membrane and supportive scaffolding
electroactive struts is to reduce the flow in the artery when the
struts. This embodiment functions in a similar manner as the
umbrella-like flow modulation assembly. As the voltage is applied,
the struts of electroactive polymer bend and contact the artery
wall, deploying the membrane in the lumen of the artery thus
reducing the cross-sectional area of the lumen available for the
blood to flow through. When the apparatus is not connected to any
external voltage source, the struts contract radially to their
former position, ending up flush against the pushwire. In this
state, blood could flow with minimum resistance. In this
embodiment, postconditioning is achieved by connecting
intermittently the voltage source to the electroactive polymer
assembly. As previously described, this step is performed following
partial or complete reperfusion of the blocked artery using a
reperfusion member. When the source is connected to the
electroactive polymer flow modulation device, the electroactive
polymer struts are bent and the membrane is deployed in the artery,
and they reduce blood flow to a near occlusion. Conversely, when
the electroactive polymer flow modulation device is disconnected
the struts and membrane are in a configuration flush to the
pushwire and flow is increased. By intermittently connecting the
voltage source, blood flow can effectively be modulated.
[0379] In some embodiments, an operator uses radiopaque markers as
reference points to monitor and gauge the position of members, the
state of member expansion, and the appropriate distances to move
the microcatheter or pushwire.
Methods of Using Primarily Electrically-Controlled Flow Modulation
Members
[0380] FIG. 50 is a process flow chart for performing
postconditioning with mechanical thrombectomy (an example of one of
the various techniques for achieving reperfusion) in accordance
with some embodiments of the present invention. For example, the
steps in FIG. 50 may be applied to assemblies with a primarily
electrically-controlled flow modulation member.
[0381] In step 5001, a large catheter (e.g., a 6 French catheter)
is inserted and guided, for example, from the femoral artery to the
neck. In step 5002, a guidewire is inserted through the large
catheter and navigated so that its distal end is at a position
distal to the location of the clot, for example, in a cerebral
artery.
[0382] In optional step 5003, an intermediate catheter (e.g., a 5
French catheter) is inserted over the guidewire and advanced so
that its distal end is at a position (e.g., the sphenoidal (M1)
segment of the middle cerebral artery) that is closer to the clot
than the distal end of the large catheter. In the event of
subsequent passes, an intermediate catheter saves time in
navigating a new guidewire from the distal end of the large
catheter to a position distal to the location of the clot.
[0383] In step 5004, a microcatheter is inserted over the guidewire
and advanced so that its distal end is at a position distal to the
clot. In step 5005, the guidewire is removed from the microcatheter
and replaced with a pushwire. Electricity may be used to control
the degree of occlusion, caused by the flow modulation member,
through various mechanisms including changing the voltage developed
across an EAP. In some embodiments, increasing the voltage
potential causes the EAP to bend outward and, spreading an
occlusive membrane outward and increasing occlusion. The pushwire
has a reperfusion member coupled near its distal end. An EAP flow
modulation member may be coupled to the pushwire. Some reperfusion
members (such as those that may have clot-capture functionality)
may have a self-expanding region adapted for engaging with a clot
(i.e., an "active region"). If using a clot-capturing reperfusion
member, the active region of the reperfusion member may be advanced
within the microcatheter so as to be adjacent to the clot. Thus,
when the microcatheter is retracted proximally to unsheathe the
reperfusion member, as in step 5006, the active region will expand
and engage with the clot. During all passes with a clot-capturing
reperfusion member, the microcatheter should be sufficiently
retracted so that the reperfusion member contacts the clot. If an
EAP flow modulation member is coupled to the pushwire, the
microcatheter should not be covering the flow modulation member (at
least at times when the flow modulation member is intended to be
expanded to occlude the artery). A control handle ("voltage
controller"), containing a voltage source such as a battery, is
affixed to the proximal end of the pushwire. By affixing the
voltage controller, the electrical connectors from the voltage
source join the wires 4940 and 4942 that develop voltage across the
EAP. A switch on the voltage controller is pressed, developing
voltage across the EAP and causing the EAP to bend outward and
spread an occluding membrane across the blood vessel. Conversely,
reducing the voltage potential contracts the occluding membrane and
unblocks the vessel.
[0384] Following step 5006, the status of reperfusion should be
assessed and the elapsed time tracked. The reperfusion status may
be assessed by, for example, injecting a contrast agent (e.g., a
bolus of radiopaque solution) through the large catheter,
microcatheter, or intermediate catheter if applicable, and
performing angiography to view the diffusion of the contrast agent.
The voltage potential through the EAP must be reduced in order to
allow the contrast agent to diffuse through the vessel. Suitable
contrast agents may include, but are not limited to, iothalamate
meglumine, diatrizoate meglumine, and other iodine-containing
solutions. If reperfusion has occurred then proceed with either (1)
postconditioning 5010, if postconditioning has not been already
performed on a prior pass; or (2) step 5011, which consists of
extracting the microcatheter and pushwire from the body, if
postconditioning was performed previously. To deliver beneficial
agents during postconditioning through the catheters, the occlusion
caused by the flow modulation member can be temporarily removed by
changing the voltage potential across the EAP in order to contract
the occluding membrane.
[0385] In step 5006, if the blood vessel has not been sufficiently
reperfused, then proceed to step 5007 where voltage potential is
developed across the EAP, thus causing occlusion of the blood
vessel. A determined period of wait-time "t" (e.g., about 5
minutes) is allowed so that the clot-capturing reperfusion member
may expand into and engage with the clot. After wait time t, the
flow modulation member is deflated and the status of reperfusion is
assessed again. If the blood vessel has not been adequately
reperfused, proceed with step 5008 where the microcatheter and
pushwire are removed. If a predetermined maximum number of passes
has not yet been completed, a new pass is initiated in step 5009
with the insertion of a new guidewire. Steps 5004-5009 are repeated
in subsequent passes until either (1) the blood vessel is
sufficiently reperfused, in which case proceed with either step
5010 if postconditioning has not been already performed or step
5011 if postconditioning performed previously, or (2) the
predetermined maximum number of passes has been completed, in which
case proceed with step 5013.
[0386] If the blood vessel is sufficiently reperfused after step
5006 or step 5007, postconditioning will be performed using the
flow modulation member unless postconditioning was performed on a
previous pass. If reperfusion is sufficient and postconditioning
has not been performed on a previous pass, the flow modulation
member is expanded and contracted in step 5010 according to a
determined series of one or more postconditioning cycles.
Sufficient voltage is maintained during the parts of the cycles
where the occlusion is desired. Beneficial agents administered
through the available catheters will be able to reach the infarct
region or clot only when the umbrella is not fully occluding the
vessel (e.g. during the reperfusion periods of the postconditioning
cycle). Examples of postconditioning cycles are described in
greater elsewhere herein.
[0387] By having the flow modulation member expanded so as to
occlude the vessel, a stable hemodynamic environment is created,
which helps minimize the risk of distal embolization. In some
embodiments, expanding the umbrella concurrently with the
deployment of the reperfusion member increases the benefits of
postconditioning by controlling when reperfusion first occurs, so
that postconditioning may be performed from the onset of
reperfusion.
[0388] Upon removal of voltage potential from the EAP, the
occlusion decrease and the flow modulation member gradually resumes
its flush configuration. The voltage potential can be removed by
causing the electrodes to disconnect from the voltage source. Upon
contraction of the flow modulation member, the occlusion is
gradually removed and the blood flow gradually restored.
[0389] If reperfusion is sufficient but postconditioning has
already been performed on a previous pass, the microcatheter and
pushwire are removed from the body in step 5011. In a given pass,
after unsheathing the clot-capturing reperfusion member in step
5006 the operator should allow the clot-capturing reperfusion
member to expand into the clot until wait time t has elapsed. To
simultaneously remove the microcatheter and pushwire, an operator
may hold the proximal ends of the pushwire and microcatheter
together and translate them proximally until they are completely
withdrawn from the body in accordance with some embodiments. The
clot-capturing reperfusion member is not resheathed in the
microcatheter during its exit from the body, but instead passes,
along with the microcatheter and pushwire, within and through the
intermediate catheter (if present) and/or the larger catheter.
Therefore, the intermediate and/or larger catheters remain in place
while the microcatheter and pushwire are removed from the body.
Optionally, suction may be applied through the larger catheter
and/or intermediate catheter to limit the dispersion of secondary
emboli.
[0390] In step 5012, an operator determines whether clot material
has been sufficiently removed by the clot-capturing reperfusion
member. The status of reperfusion may inform this inquiry. Thus, in
some embodiments, the status of reperfusion is assessed by, for
example, injecting a contrast agent through the large catheter and
performing angiography to view the diffusion of the contrast agent.
In some embodiments, the reperfusion member itself is inspected
(e.g., visually) to determine whether the degree of retrieved clot
material is sufficient. Sufficiency may depend on numerous factors
including, but not limited to, changes in perfusion.
[0391] Following step 5012, if a sufficient amount of clot material
has been retrieved, as evidenced in some embodiments by the status
of reperfusion, the procedure is completed and any remaining
catheters are removed from the body according to step 5013.
However, if none or an insufficient amount of clot material has
been retrieved, and if a predetermined maximum number of passes has
not yet been completed, a new pass is initiated in step 5009 with
the insertion of a new guidewire.
Reperfusion Members
[0392] Embodiments of the reperfusion member allow an operator to
treat a clot or embolus, usually to effectuate reperfusion.
Examples of such treatment include removal (of all, part, or
multiple pieces of the clot or embolus), maceration, lysis,
compression, pushing, pulling, moving, dissolving, or maintaining
in situ. According to some embodiments, a reperfusion member may
resemble or comprise expandable stent technology, a corkscrew, a
jackhammer, a lasso, a loop, a parachute, a filter, a cheese
slicer, a vacuum, an inflatable object, a fishing net, a bottle
brush, and/or ultrasound technology. The choice of a reperfusion
member may depend on the conditions of a specific occluded blood
vessel.
[0393] In certain embodiments, a reperfusion member may have acting
components that are partially or entirely non-mechanical in nature.
A reperfusion member may contain for release or be coated by
chemical, pharmaceutical or other particular agents, which may act
to, for example, lubricate the member, dissolve a clot, loosen a
clot, cause a clot to contract, or increase the bonding of a clot
with the reperfusion member. Such agents may also act on tissue
surrounding a clot to, for example, vacillate, heal, minimize
reperfusion injury, or minimize infarct size.
[0394] According to a preferred embodiment, a reperfusion member is
based on retrievable stent technology. Retrievable stent technology
is especially effective at achieving desired patient outcomes
because of its ability to successfully enmesh and drag out large
portions of clots. Retrievable stents may also be self-expanding
and self-conforming to the size and shape of the blood vessel
lumen, thus increasing the simplicity and safety of a
clot-capturing reperfusion member. Generally, the central body
(i.e., the part most likely to contact the clot) of a
clot-capturing reperfusion member may be cylindrical. The central
body may be connected to a pushwire by a plurality of struts. Both
the proximal end and/or distal end may be either open, closed,
tapered, and/or connected to a pushwire while maintaining an
expandable cell structure. In some embodiments, the central body
wraps around itself.
[0395] FIG. 51A illustrates an embodiment of the clot-capturing
reperfusion member with a central body 5100 and closed distal end,
both attached to a pushwire 106. Alternatively, FIG. 51B
illustrates an embodiment of the clot-capturing reperfusion member
with a central body 5100 and an open distal end 5104. FIG. SIC
illustrates an embodiment of the clot-capturing reperfusion member
with a central body 5100 and a plurality of struts 5106. Finally,
FIG. 52 illustrates an embodiment of the clot-capturing reperfusion
member with a central body that is not connected but wraps around
itself 5200. This can be useful for a reduced profile for delivery,
expansion of the reperfusion member, among other clinical
benefits.
[0396] The preferred dimensions of a clot-capturing reperfusion
member may be varied depending on, among other factors, the radius
of the blood vessel, the radius of the clot, and the consistency or
resistance of the clot. For example, the length of a clot-capturing
reperfusion member may range from about 1 cm to 5 cm. At full
expansion, the radius of a clot-capturing reperfusion member may
range from about 1 mm to 4 mm.
[0397] The latitudinal resistive force may vary according to, among
other factors: the dimensions of the clot-capturing reperfusion
member, the dimensions of the struts, and the density of the cells.
In addition, the latitudinal resistive force may change as the
clot-capturing reperfusion member expands. Different latitudinal
resistive properties may be desirable depending on the condition of
the patient and of the clot.
[0398] In some embodiments, a clot-capturing reperfusion member is
manufactured in a manner similar to a neurovascular stent, that is,
the pattern of struts is laser-cut from a tube of suitable
material, such as nitinol, and then electro-polished. Generally,
embodiments of the clot-capturing reperfusion member may be
manufactured using methods and materials described above or known
in the art. In preferred embodiments, the expandable cell structure
is made from a single piece of nitinol; however, separate pieces
and other shape-memory materials, shape-memory alloys, or other
super-elastic materials that tend to exert pressure to expand to
their set shape may be used (e.g., nickel titanium alloy, stainless
steel, or cobalt chrome alloy).
[0399] An alternative way of making the clot-capturing reperfusion
member is to use separate pieces and attached them using a method
such as soldering. Wires, struts, and cell components may be first
cut as separate parts and then attached.
[0400] The proximal ends of the clot-capturing reperfusion member
are attached to the pushwire in a similar manner as the umbrella's
struts. In one attachment solution, an attachment ring 110
(illustrated in FIG. 34) may be a separate piece and made of a
material such as steel. The steel attachment ring is compressed,
using swaging, over the ends of the clot-capturing reperfusion
member is struts and the pushwire. Swaging creates even sealing
without heating the nitinol, which would potentially alter the
clot-capturing reperfusion member's shape memory.
[0401] Radiopaque materials may be used to determine relative
position, measure expansion, and gauge degree of clot entrapment.
Radiopaque materials may include platinum, cobalt, molybdenum,
gold, silver, tungsten, iridium, polymers, and combinations of
various materials. In a preferred embodiment, as shown in FIG. 53,
radiopaque markers 5302 are attached to the proximal and distal
ends of a reperfusion member, and select cell segments running
longitudinally through the central body are covered with a
radiopaque coating 5304.
Cell Structures
[0402] Denser clots may and often do require multiple passes. This
means that several unsuccessful--and time consuming--attempts are
made to redeploy the device against the clot. A clot-capturing
reperfusion member exerting greater radial force could help the
member to grip the clot. A hexagonal cell structure may provide the
right amount radial force. The wider angles of a hexagon (in
comparison to a diamond) allow the clot-capturing reperfusion
member to push against and into the clot more strongly, while still
affording enough flexibility to be sheathed within the
microcatheter.
[0403] The central body of a clot-capturing reperfusion member may
be composed of various cell structures. Different cell geometries
and dimensions (e.g., length, diameter, and pressure) may influence
the extent and facility with which a clot-capturing reperfusion
member engages with a clot. For example, larger cells, especially
cells with narrower clot-facing width, may cut through a clot more
easily. Meanwhile, smaller cells, especially cells with greater
non-clot facing depth, may exert more overall pressure on a clot,
tending to compress the clot against the blood vessel wall.
Therefore, different cell geometries and dimensions may be desired
for different situations, sizes and locations of clots or
emboli.
[0404] FIG. 54 illustrates a preferred embodiment of the
clot-capturing reperfusion member with a central body 5402 having a
cylindrical structure with a plurality of individual cells 5404.
According to some embodiments, the cell pattern may include a
hexagon 5510 (shown in FIG. 55A), a quadrilateral 5512 (shown in
FIG. 55B), a circle 5514 (shown in FIG. 55C), and/or an oval 5516
(shown in FIG. 55D). Accordingly, as shown by a two-dimensional
diagram in FIG. 56, a cell structure pattern may include
diamond-shaped cells 5602. In some embodiments, the cell structure
pattern may resemble off-cycle wave curves. Among the above,
embodiments with a hexagonal cell structure, as shown in FIG. 54,
may provide superior radial force. A two-dimensional diagram of the
same hexagonal cell pattern is shown in FIG. 57. Although the
number and dimensions of the cells may vary, the length of one side
5702 of a hexagonal cell 5704 in the illustrated embodiment is 1.8
mm. In other embodiments, the cells may be stretched so that the
cells are longer across the central longitudinal axis than they are
wide.
[0405] Connecting junctions and other thicker parts of cells in a
clot-capturing reperfusion member may be used and enhanced to
facilitate clot adhesion to the member. FIG. 58 illustrates a strut
junction 5802 with a greater radius than other parts of the struts
and thicker parts, which may be on the outside 5804, the inside
5806, or both 5808 sides of a cell.
Strut Cross-Sections
[0406] According to some embodiments, the cross-sectional shape and
dimensions of the struts in a reperfusion member may vary, both in
general and within the same member. For example, the cross-sections
of the struts in a reperfusion member may be circular, oval, or
rectangular. In a preferred and particularly innovative embodiment,
a reperfusion member uses an arrowhead-shaped strut cross-section
to provide significant advantages for clot and embolus
retrieval.
[0407] The strut cross-sections in a reperfusion member may affect
the quality of its engagement with a clot. If a clot does not
sufficiently adhere to a reperfusion member, multiple passes of the
member may be required, thus complicating and prolonging the
procedure. Even multiple passes do not guarantee successful
engagement with a clot and may increase the risks, such as brain
damage, associated with stroke. Furthermore, if a clot sufficiently
adheres to a reperfusion member then emboli may be less likely to
break away, migrate downstream, and irretrievably block smaller
blood vessels.
[0408] In preferred embodiments, the reperfusion member has
arrowhead-shaped strut cross-sections. Similar to how an arrowhead
used for hunting pierces its target easily but is then difficult to
dislodge, an arrowhead-shaped, or generally triangular, profile
facilitates trapping a clot within the reperfusion member by
piercing the clot yet providing more resistance to grip the clot
after penetration and during retrieval. In most embodiments, the
smallest angle (i.e., sharpest point) of the triangular
cross-section points laterally outward toward the blood vessel wall
(and clot) to facilitate clot penetration.
[0409] Numerous variations of an arrowhead-shaped or triangular
cross-section may be used, with a few of these modifications
exhibited in the embodiments of FIGS. 59A-59K. First, FIG. 59A
illustrates an isosceles-triangle embodiment where the lengths of
two sides 5900 and the other side 5902 of a triangular
cross-section are, for example, 70 .mu.m and 50 .mu.m respectively.
The attacking tip of the strut i.e., the edge that touches first
the clot is depicted by reference numeral 5904. FIG. 59B
illustrates an arrowhead-shaped embodiment with the same
cross-section as the isosceles triangle except for a bend 5906 in
the shorter side to increase the width of the inner side of the
reperfusion member's struts. By providing more contact area on the
inside of a reperfusion member, clot adhesion and compression may
be improved. The same is true for other embodiments with
cross-sections having wider base sides, such as the
equilateral-triangle embodiment shown in FIG. 59C, the compressed
isosceles-triangle embodiment shown in FIG. 59D, the
isosceles-trapezoid embodiment shown in FIG. 59E (which may have a
flattened surface 5910), the concave equilateral-triangle
embodiment shown in FIG. 59I, the concave isosceles-trapezoid
embodiment shown in FIG. 59J, and the concave half-oval embodiment
shown in FIG. 59K. In particular, those embodiments with
cross-sections having a bended or concave surface facing the
reperfusion member's central longitudinal axis may further prevent
a clot from migrating away from the member.
[0410] Next, FIG. 59F illustrates an isosceles-triangle embodiment
where the smallest angle (i.e., point of greatest curvature
sharpest point) 5908, which points laterally outward toward the
blood vessel wall, has been dulled. By rounding the sharp edges of
a reperfusion member in a process such as electro-polishing, trauma
to the blood vessel walls is minimized. The same is true for other
embodiments with cross-sections having dulled points 5908, such as
the half-circle embodiment shown in FIG. 59G, the half-oval
embodiment shown in FIG. 59H, and the concave half-oval embodiment
shown in FIG. 59K.
[0411] FIG. 60A illustrates a hexagonal cell for an embodiment of
the reperfusion member with the isosceles-triangle cross-section
shown in FIG. 59A. In addition, FIG. 60B shows a three-dimensional
section of strut with the same isosceles-triangle cross-section.
The above modifications to the cross-sections may be used alone or
in combination in a reperfusion member and/or a single strut of a
reperfusion member.
[0412] Embodiments of the flow modulation system and its components
may be used to perform reperfusion and/or postconditioning
procedures. In one embodiment as shown in FIG. 61A, an operator may
push a guidewire (not shown in the FIG. 61A), a microcatheter 6102
to a location proximal to a clot 6100 (also identified by reference
numeral 4710 in earlier illustrations) in a blood vessel 6101.
Then, in FIG. 61B, the operator may push the microcatheter 6102
past the clot 6100 so that the distal end of the microcatheter is
distal to the clot. Often, the microcatheter 6102 follows the path
of least resistance and maneuvers around the clot 6100 (as shown in
FIG. 61C), wedging itself between the clot and the blood vessel
wall 6101 (also reference numeral 114 in earlier illustrations),
rather than passing directly through the clot. A pushwire 6106 with
a flow modulation member 6112 and a reperfusion member 6110 may be
positioned within the microcatheter 6102. In this embodiment the
reperfusion member is a clot-capturing reperfusion member. However,
various types of reperfusion members may be used. The operator may
pull the microcatheter 6102 back (as shown in FIG. 61D) while the
pushwire 6106 is held in place, unsheathing both the reperfusion
member 6110 and the flow modulation member 6112, which self-expands
to occlude blood flow. Meanwhile, the reperfusion member 6110 (also
reference numeral 108 in earlier illustrations), which
substantially spans the clot 6100 when unsheathed, may begin to
self-expand (as shown in FIG. 61E), compressing the clot against
the opposing wall of the blood vessel and reopening the occluded
vessel for blood flow. Postconditioning may be performed at this
point when recanalization first occurs.
[0413] The operator may push the microcatheter 6102 to partially
re-sheathe (as shown in FIG. 61F) the flow modulation member 6112
and cause reperfusion. The operator may continue to pull (to deploy
the flow modulation member 6112 and decrease flow) and push (to
constrain the flow modulation member 6112 and increase flow) the
microcatheter 6102, while holding the pushwire 6106 still, to
cyclically modulate blood flow and achieve sufficient
postconditioning before allowing natural reperfusion. The operator
may facilitate these movements by using a handle or control member,
as would be understood by those skilled in the art. The flow
modulation member 6112 may be either opened or closed before
reperfusion begins; however, in a preferred method, the flow
modulation member is opened before reperfusion for more precise
control over, and knowledge of when, reperfusion and
postconditioning begins.
[0414] According to an embodiment using the flow modulation member
shown in FIG. 27A-27C, described previously, an operator could push
the associated microcatheter forward by about 3 mm to transition
from having the modulation member fully deployed (blocking blood
flow) to having the modulation member completely resheathed
(allowing blood flow). In some embodiments, an operator may leave
or hold the flow modulation member partially, or not fully,
deployed to allow limited blood flow or to minimize friction with
the blood vessel wall.
Examples of Postconditioning Cycles
[0415] The number and length of the time intervals for
postconditioning may vary as determined by the operator. In FIG.
62A-62J, the y-axis represents the percentage of the
cross-sectional luminal area of the blood vessel spanned by the
flow modulation member normalized to its constrained state.
Therefore, this graph does not take into account the effect of the
clot or changes in unblocked space around the clot (i.e., if the
flow modulation member is expanded so that it is stretches across
75% of the blood vessel, than the graph at that point in time is
75% shaded.) The x-axis is time in seconds. For example, the
operator may choose more and/or longer cycle periods when the time
from the onset of the ischemia is greater. An example of a
desirable interval schedule may be about 6 alternating intervals of
approximately 30 seconds unblocked 6200 and 30 seconds blocked
6202, as shown in FIG. 62B.
[0416] FIG. 62A is an example of an interval schedule with 3
alternating intervals of approximately 60 seconds unblocked and 60
seconds blocked. The transitions from unblocking to blocking as
well as the transitions from blocking to unblocking occur rapidly
as is indicated by the vertical slope on either side of the shaded
(blocking) areas.
[0417] FIG. 62C is an example of an interval schedule with 1
alternating interval of approximately 600 seconds (ten minutes)
unblocked and 600 seconds blocked. The transitions from unblocking
to blocking as well as the transitions from blocking to unblocking
occur rapidly as is indicated by the vertical slope on either side
of the shaded (blocking) area.
[0418] FIG. 62D is an example of where the unblocked time is not
equal to the blocked time, within the cycles. The different parts
of the cycle can be of disparate time spans and may vary across
cycles as well. The example depicted in FIG. 62D shows an interval
schedule with 3 alternating intervals of approximately 30 seconds
unblocked and 15 seconds blocked. The transitions from unblocking
to blocking as well as the transitions from blocking to unblocking
occur rapidly as is indicated by the vertical slope on either side
of the shaded (blocking) areas.
[0419] FIG. 62E is an example of an interval schedule with 3
alternating intervals of approximately 15 seconds unblocked and 15
seconds blocked. The transitions from unblocking to blocking as
well as the transitions from blocking to unblocking occur rapidly
as is indicated by the vertical slope on either side of the shaded
(blocking) areas.
[0420] FIG. 62A is an example of an interval schedule with 3
alternating intervals of approximately 60 seconds unblocked and 60
seconds blocked. The initial transition from blocking to unblocking
is gradually (as indicated by the curved slope). Two possibilities
explaining why this gradual reperfusion may occur are as follows: A
first possibility is that the flow modulation member is not
deployed as the reperfusion member gradually allows an increasing
amount of flow through the vessel. A second possibility is that the
flow modulation member is deployed as the reperfusion member
expands. The flow modulation member gradually allows for an
increase in flow at the beginning of postconditioning.
[0421] FIG. 62G is an example of an interval schedule where the
flow modulation member steadily increases blocking at the beginning
of the blocking portion of each cycle. The transitions from
blocking to unblocking occur rapidly as is indicated by the
vertical slope on the right-hand sides the shaded (blocking)
areas.
[0422] FIG. 62H is an example of an interval schedule where the
transitions from unblocking to blocking as well as the transitions
from blocking to unblocking occur gradually as is indicated by the
curved slope on either side of the shaded (blocking) areas.
Additionally there is not a substantial period of unblocking
between intervals.
[0423] FIG. 62I is an example of an interval schedule where the
transitions from blocking to unblocking occur gradually as is
indicated by the curved slope on the right-hand side of the shaded
(blocking) areas. However, the transitions from unblocking to
blocking occur rapidly. Gradual or partial occlusion with a flow
modulation member may be used with the examples shown in FIGS.
62F-62J. In particular, FIG. 62J shows a postconditioning schedule
where the degree of occlusion is non-linear. Meanwhile, the flow
modulation member is deployed gradually for slower and steadier
occlusion of a blood vessel, as can be seen from the progressive
occlusion values in FIG. 62J. Postconditioning is preferred to be
performed as close to the onset of reperfusion as possible. The
actual degree of reperfusion achieved, as compared to normal flow
rates, may vary depending on the degree to which reperfusion is
achieved by the reperfusion member or the degree to which occlusion
is achieved by the flow modulation member.
[0424] Each of the Embodiments of the flow modulation system or
devices may also be used with chemicals, pharmaceuticals, or other
agents to, for example: further minimize reperfusion injury, aid in
removing a clot, or otherwise benefit a patient's condition. Agents
that may minimize reperfusion injury include cyclosporine,
sodium-calcium Na2+/Ca2+ exchange inhibitors, monoclonal
antibodies, temperature reducing agents, or agents that slow cell
metabolism. Agents that may aid in removing a clot include tPA and
other agents that aid in dissolving, dislodging, or macerating
clots. Agents that may otherwise benefit the patient's condition
include pharmaceuticals commonly used for treating clots; agents
for treating clots, preventing restenosis, or that commonly coat
intravascular devices such as vasodilators; nimodipine; sirolimus;
paclitaxel; anti-platelet compounds; agents that promote the
entanglement or attachment of a clot with a reperfusion member; and
anticoagulants such as heparin.
[0425] Any patents, publications, or other references mentioned in
this application for patent are hereby expressly incorporated by
reference.
[0426] As will be apparent to one of ordinary skill in the art from
a reading of this disclosure, the present disclosure can be
embodied in forms other than those specifically disclosed above.
The particular embodiments described above are, therefore, to be
considered as illustrative and not restrictive. Those skilled in
the art will recognize, or be able to ascertain, using no more than
routine experimentation, numerous equivalents to the specific
embodiments described herein. The scope of the present invention is
as set forth in the appended claims and equivalents thereof, rather
than being limited to the examples contained in the foregoing
description.
* * * * *