U.S. patent application number 12/574103 was filed with the patent office on 2010-01-28 for devices and methods for disruption and removal of luminal occlusions.
This patent application is currently assigned to UNIVERSITY OF FLORIDA RESEARCH FOUNDATION, INC.. Invention is credited to Christopher D. Batich, Eric Eskioglu, Robert A. Mericle, Swadeshmukul Santra, Jessie T. Stanley.
Application Number | 20100023038 12/574103 |
Document ID | / |
Family ID | 33452359 |
Filed Date | 2010-01-28 |
United States Patent
Application |
20100023038 |
Kind Code |
A1 |
Santra; Swadeshmukul ; et
al. |
January 28, 2010 |
DEVICES AND METHODS FOR DISRUPTION AND REMOVAL OF LUMINAL
OCCLUSIONS
Abstract
The subject invention pertains to an elastic sheath, device, and
methods for disrupting and/or removing occlusive material from
lumens, particularly biological lumens, such as the vasculature,
ureter, urethra, fallopian tubes, bile duct, intestines, and the
like. The subject invention provides for effective disruption and
removal of occlusive material, such as a thrombus, from the body
lumen with minimal risk of injury to the lumen wall.
Advantageously, the invention can be used to achieve a high degree
of removal while minimizing the amount of occlusive material that
is released into the body lumen. The subject invention further
pertains to methods for disrupting and removing occlusive material
from a biological lumen. In another aspect, the present invention
concerns a device useful as an in vitro model of luminal occlusion
and methods for using the device to test the efficacy of devices
and methods for treating luminal occlusions.
Inventors: |
Santra; Swadeshmukul;
(Orlando, FL) ; Mericle; Robert A.; (Brentwood,
TN) ; Batich; Christopher D.; (Gainesville, FL)
; Stanley; Jessie T.; (Trenton, FL) ; Eskioglu;
Eric; (Nashville, TN) |
Correspondence
Address: |
SALIWANCHIK LLOYD & SALIWANCHIK;A PROFESSIONAL ASSOCIATION
PO Box 142950
GAINESVILLE
FL
32614
US
|
Assignee: |
UNIVERSITY OF FLORIDA RESEARCH
FOUNDATION, INC.
Gainesville
FL
|
Family ID: |
33452359 |
Appl. No.: |
12/574103 |
Filed: |
October 6, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10844737 |
May 12, 2004 |
7618434 |
|
|
12574103 |
|
|
|
|
60470067 |
May 12, 2003 |
|
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Current U.S.
Class: |
606/159 |
Current CPC
Class: |
A61B 2017/2212 20130101;
A61B 17/221 20130101; A61B 17/320725 20130101 |
Class at
Publication: |
606/159 |
International
Class: |
A61B 17/22 20060101
A61B017/22 |
Claims
1. A device for occlusion removal and/or disruption comprising: a
rod; an elastic sheath that ensheaths a segment of said rod,
wherein said sheath has a plurality of slits; and means for
expanding said elastic sheath, and wherein said elastic sheath is
displaced from said segment of said rod when said expansion means
is activated, and wherein said rod and said elastic sheath
cooperate to form a compartment when said expansion means is
activated.
2. The device of claim 1, wherein said expansion means comprises an
expandable balloon, wherein at least a portion of said expandable
balloon is covered by said elastic sheath.
3. The device of claim 1, wherein said plurality of slits are
longitudinally arranged around at least a portion of the
circumference of said elastic sheath, and wherein each slit is
separated from adjacent slits by a longitudinal band of elastic
material.
4. The device of claim 3, wherein said longitudinal bands are
cross-linked with a plurality of lateral bands that bridge said
longitudinal slits, thereby forming a mesh.
5. The device of claim 2, wherein said expandable balloon comprises
at least one radially constrained portion and at least one radially
unconstrained portion.
6. The device of claim 5, wherein when pressure is applied to said
expandable balloon, said at least one radially unconstrained
portion expands to form at least one sphere or spheroid shape.
7. The device of claim 6, wherein said at least one radially
constrained portion is constrained with a fiber that is wrapped
around said at least one radially constrained portion.
8. The device of claim 6, wherein the compartment is substantially
conical in shape.
9. The device of claim 1, wherein the elastic sheath comprises a
flexible polymer tube.
10. The device of claim 1, wherein the elastic sheath comprises a
thermoplastic elastomer.
11. The device of claim 1, wherein the elastic sheath comprises a
flexible polymer selected from the group consisting of silicone,
polyurethane, silicone-polyurethane copolymer, and
styrene-ethylene-butylene-styrene (copolymer).
12. The device of claim 1, wherein said device is at least
partially composed of an imageable material.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] The present application is a divisional of U.S. patent
application Ser. No. 10/844,737, filed on May 12, 2004, which
claims the benefit of U.S. Provisional Application Ser. No.
60/470,067, filed May 12, 2003. Each of these applications is
incorporated by reference herein in its entirety, including any
figures, tables, nucleic acid sequences, amino acid sequences, or
drawings.
BACKGROUND OF THE INVENTION
[0002] The blockage of human arteries can lead to a variety of
serious medical complications. Arterial blockages reduce blood flow
through the affected artery and may result in damage to the tissue
that is relying upon the blood's supply of oxygen (ischemia). For
example, if the blockage is in an artery that supplies blood to the
heart itself, a heart attack may result.
[0003] Thrombosis and atherosclerosis are common ailments that
result from the deposition of thrombus on the walls of blood
vessels. When such deposits harden, they are commonly referred to
as plaque. These plaque deposits occur commonly in blood vessels
that feed the brain, heart, and limbs of the human body. Stasis,
incompetent valves, and trauma in the venous circulation are common
causes of thrombosis, which can often manifest as a deep vein
thrombosis in the peripheral vasculature. When such deposits
build-up in localized regions of the blood vessel, they can
restrict blood flow and cause a serious health risk.
[0004] In addition to forming in the natural vasculature,
thrombosis is a serious problem in "artificial" blood vessels,
particularly in peripheral femoral-popliteal and coronary bypass
grafts and dialysis access grafts and fistulas. The creation of
such artificial blood vessels requires anastomotic attachment at
one or more locations in the vasculature. Such sites are
particularly susceptible to thrombus formation due to narrowing
caused by intimal hyperplasia, and thrombus formation at these
sites is a frequent cause of failure of the implanted graft or
fistula. The arterio-venous grafts and fistulas that are used for
dialysis access are significantly compromised by thrombosis at the
sites of anastomotic attachment and elsewhere. Thrombosis often
occurs to such an extent that the graft needs to be replaced within
a few years or even a few months.
[0005] A variety of methods have been developed for treating
thrombosis and atherosclerosis in the coronary and peripheral
vasculature as well as in implanted grafts and fistulas. Such
techniques include pharmacologic thrombolytic therapy, given either
intravenously or intra-arterially (Hacke W. et al., JAMA,
274:1017-1025, 1995; del Zoppo G. J. et al., Stroke, 29:4-11,
1998), surgical procedures, such as coronary artery bypass
grafting, and minimally invasive procedures, such as angioplasty
atherectomy, transmyocardial and revascularization. In particular,
a variety of techniques generally referred to as "thrombectomy"
have been developed. Thrombectomy generally refers to procedures
for the removal of relatively soft thrombus and clot from
vasculature. Removal is usually achieved by mechanically disrupting
the clot, and can optionally include the administration of
thrombolytic agents. The disrupted thrombus or clot is then
withdrawn through a catheter, typically with a vacuum or mechanical
transport device.
[0006] Thrombectomy generally differs from angioplasty and
atherectomy in the type of occlusive material that is being treated
and in the level of care taken to avoid damage to the blood vessel
wall. The material removed in most thrombectomy procedures is
relatively soft, such as the clot formed in deep vein thrombosis,
and is usually not hardened plaque of the type treated by
angioplasty in the coronary vasculature. Moreover, it is usually an
objective of thrombectomy procedures to have minimum or no
deleterious interaction with the blood vessel wall. Ideally, the
clot will be disrupted and pulled away from the blood vessel wall
with no harmful effect on the wall itself.
[0007] While successful thrombectomy procedures have been achieved,
most have required compromise between the competing objectives of
removing the thrombosis and minimizing injury to the blood vessel
wall. While more aggressive thrombectomy procedures employ rotating
blades that can be very effective at thrombus removal, they present
a significant risk of injury to the blood vessel wall.
Alternatively, those procedures that rely primarily on vacuum
extraction together with minimum disruption of the thrombus, often
fail to achieve sufficient thrombus removal.
[0008] U.S. Pat. No. 5,904,698 describes a catheter having an
expandable mesh with a blade or electrode for shearing obstructive
material, which penetrates the mesh when the mesh is expanded in a
blood vessel. Other catheters having expandable meshes, cages,
and/or shearing elements are described in U.S. Pat. Nos. 5,972,019;
5,954,737; 5,795,322; 5,766,191; 5,556,408; 5,501,408; 5,330,484;
5,116,352; and 5,410,093; and WO 96/01591. Catheters with helical
blades and/or Archimedes screws for disrupting and/or transporting
clot and thrombus are described in U.S. Pat. Nos. 5,947,985;
5,695,501; 5,681,335; 5,569,277; 5,569,275; 5,334,211; and
5,226,909. Other catheters of interest for performing thrombectomy
and other procedures are described in U.S. Pat. Nos. 5,928,186;
5,695,507; 5,423,799; 5,419,774; 4,762,130; 4,646,736; and
4,621,636. Techniques for performing thrombectomy are described in
Sharafudin et al. (JVIR 8:911-921, 1997) and Schmitz-Rode et al.
(Radiology 180:135-137, 1991).
[0009] One of the problems with many of these devices, however, is
that particulate matter (e.g., thrombus, atheroma, or other embolic
or occlusive material) may be released from the wall of the vessel
during the procedure. If such particulate matter travels
downstream, it may become lodged or otherwise harm the patient. For
example, ischemic stroke may occur when such emboli are released in
the carotid or cerebral arteries and travel to the patient's brain.
To prevent or minimize damage from emboli, vascular filters have
been suggested that are typically disposed on a device such as a
catheter, guidewire, or sheath. These devices may be introduced
within a blood vessel downstream of a location being treated, and
the filter on the device deployed across the vessel to capture
embolic material released during the procedure. Upon completion of
the procedure, the filter may be collapsed, trapping emboli
therein, and then the device may be removed from the patient.
Catheters having expandable filters at their distal ends are
described in U.S. Pat. No. 4,928,858 and PCT publications WO
99/44542 and WO 99/44510.
[0010] The United States Food and Drug Administration (FDA) has
approved a total of eight mechanical thrombectomy devices (MTDs)
for use in thrombosed hemodialysis grafts (Kasirajan K. et al, J.
Vase. Interv. Radiol, 2001, 12:405-411). Generally, the approved
MTDs can be classified into two categories: (i) mechanical lysis
only (non-aspirating) devices and (ii) mechanical and aspirating
devices. The AMPLATZ thrombectomy device (CLOT BUSTER; MICROVENA,
White Bear Lake, Minn.), ARROW-TREROTOLA PTD (ARROW INTERNATIONAL,
Reading, Pa.), and CASTANEDA OVER-THE-WIRE BRUSH (MICRO
THERAPEUTICS, Aliso Viego, Calif.) are categorized mechanical
non-aspirating devices and ANGIOJET (POSSIS MEDICAL; Minneapolis
Minn.), GELBFISH-ENDOVAC (BOSTON SCIENTIFIC/MEDI-TECH, Brooklyn,
N.Y.), HYDROLYSER(CORDIS, Miami, Fla.), OASIS (BOSTON
SCIENTIFIC/MEDI-TECH, Watertown, Mass.) are categorized under
mechanical aspirating devices. The ANGIOJET LF140 (POSSIS MEDICAL,
Minneapolis, Minn.) is the only FDA approved device for use in
peripheral arterial occlusive disease. These devices are currently
being used or undergoing clinical evaluation for the treatment of
acute and chronic limb-threatening ischemia.
[0011] Stroke is characterized by a sudden loss of blood supply to
the brain, which results in loss of neurological function. Stroke
is the third leading cause of death in the United States (150,000
cases per year) and the leading cause of adult disability ("2002
Heart and Stroke Statistical Update", American Heart Association,
Dallas, Tex., 2001). Approximately 700,000 strokes occur annually
in the U.S., accounting for costs of over $26 billion/year for
treatment and rehabilitation. Stroke is currently classified into
two categories: hemorrhagic and ischemic. Ischemic stroke is the
most common type and accounts for 85% of all stroke cases. Ischemic
stroke (i.e., thromboembolic stroke) occurs when arteries supplying
blood to the brain are occluded by thrombus or other embolic
material (e.g., calcifications, cholesterol, plaque, etc.).
[0012] Current treatment modalities include pharmacologic
thrombolytic therapy; however, all thrombolytic drugs are not
indicated for all stroke victims and are not effective for all
thromboembolic occlusions. The treatment of ischemic stroke
patients with tissue plasminogen activator (tPA) is currently the
only FDA approved treatment in the United States. However, tPA has
been shown to benefit patients only if administered within a 3 hour
time window after the onset of neurological symptoms. Therefore, a
poor success rate in treatment of stroke is observed. Moreover, the
use of tPA is associated with a high risk of hemorrhage and cannot
be given to all patients. Endovascular mechanical thrombolytic
devices could be used to treat ischemic stroke patients less
invasively and more effectively. Unfortunately, there currently
exists no FDA approved device for ischemic stroke treatment.
Mechanical thrombectomy devices may increase the risk of arterial
performation, dissection, or endothelial injury, which can result
in intracranial hemorrhage and worsening of neurological deficits,
for example. Therefore, making such devices that will eliminate or
even reduce these risks is an extremely challenging task. For
example, a device adapted to treat ischemic stroke should be
miniaturized to fit inside intracranial arteries, which are
relatively small (1 mm to 3.5 mm in diameter). Intracranial
arteries are fragile and tortuous; therefore, the device should
also be highly flexible and maneuverable. The use of such devices,
along with tPA, may benefit patients by providing a quick recovery
from ischemic stroke.
[0013] Preliminary studies on the safety, efficacy, and device
limitations have spurred an interest in percutaneous techniques for
thrombus debulking as stand-alone therapy or as an adjunct to
pharmacologic thrombolysis. The devices have various mechanisms or
combinations of mechanisms to optimize thrombus removal. Efficacy
of thrombus removal is balanced by the propensity for vessel wall
damage and distal embolization, especially for vessel wall-contact
devices.
[0014] Therefore, there is a need for a device that is simple in
design and is highly maneuverable to permit navigation through
various lumen systems of the body, such as the intracranial,
urinary, biliary, bronchial, and coronary systems, thereby
facilitating effective disruption and removal of occlusive material
while minimizing the risk of injury to the lumen wall.
BRIEF SUMMARY OF THE INVENTION
[0015] The subject invention concerns a device and methods for
disrupting and/or removing occlusive material from lumens, such as
biological lumens within the body. Although the subject invention
is particularly useful for the disruption and/or removal of
thrombus from the vasculature, it is also applicable in other
lumens of the body, such as the ureter, urethra, fallopian tubes,
bile duct, intestines, and the like. The subject invention provides
for effective disruption and/or removal of the occlusive material
from the body lumen with minimal risk of injury to the lumen wall.
Advantageously, the invention can be used to achieve a high degree
of removal while minimizing the amount of occlusive material that
is released into the body lumen. This is particularly desirable in
treatment of the vasculature, where the release of emboli can be a
serious risk to the patient. As described in detail below, the
present invention employs a cutting means for disrupting the
thrombus, clot, embolic agent, or other occlusive material.
[0016] The present invention relates to an elastic sheath used for
constructing occlusion disruption and/or removal devices of the
invention (also referred to herein as a "thrombectomy device" or
"thrombolysis device"). The present invention further relates to a
device for occlusion removal and/or disruption comprising a rod, an
elastic sheath that ensheaths a segment of the rod, wherein the
sheath has a plurality of slits, and means for expanding the
elastic sheath, wherein the elastic sheath is displaced from the
segment of the rod when the expansion means is activated, and
wherein the rod, the expansion means, and the elastic sheath
cooperate structurally and/or functionally to form a compartment
when the expansion means is activated. Preferably, the expansion
means is an expandable balloon and the elastic sheath covers at
least a portion of the expandable balloon and at least a segment of
the rod adjacent to the expandable balloon.
[0017] The elastic sheath has a plurality of slits, with each slit
separated from the adjacent slit by a band of elastic material.
When the expansion means is activated, the slits expand and a
compartment (also interchangeably referred to herein as the "cage")
is formed through the cooperation of the rod, the elastic sheath,
and the expansion means, together. When the expansion means is an
expandable balloon, the balloon can be expanded by applying
pressure from within the balloon, such as air or saline pressure,
for example. The device can be at least partially composed of an
imageable material such that the position of the device within
biological tissue, such as a biological lumen, can be readily
determined using the appropriate sensing equipment. Therefore, it
is possible to accurately guide the device to a particular lumen
within biological tissue, and to guide the device to an occluded
area within the lumen for subsequent disruption and/or removal of
the occlusive material.
[0018] In another aspect, the subject invention pertains to a
method for disrupting and/or removing occlusive material from a
biological lumen by inserting the device of the invention into the
lumen, placing the device at a point adjacent to the occlusion,
activating the expansion means, and operating the device in a
back-and-forth motion such that the occlusion is mechanically
disrupted by abrasive contact with the bands of the elastic sheath,
and occlusive debris passes through the expanded slits, and is
thereby captured within the cage of the elastic sheath. Optionally,
the expansion means can be deactivated in order to narrow or close
the slits (collapsing the cage), to more securely contain the
occlusive debris between the bands of the elastic sheath and the
rod. In embodiments where the expansion means is an expandable
balloon, the balloon can be partially or entirely deflated in order
to narrow or close the slits and collapse the cage around the
rod.
[0019] In another aspect, the present invention concerns an in
vitro model of luminal occlusion and methods for using the in vitro
model to test the efficacy of devices and methods for treating
luminal occlusions.
BRIEF DESCRIPTION OF THE DRAWINGS
[0020] The patent or application file contains at least one drawing
executed in color. Copies of this patent or patent application
publication, with color drawing(s), will be provided by the Office
upon request and payment of the necessary fee.
[0021] FIG. 1A shows a side view of an elastic sheath constructed
in accordance with the present invention, with the placement site
of the balloon within the distal end of the elastic sheath. When
this embodiment of the elastic sheath is utilized, one conical cage
structure can be formed when the underlying balloon is activated at
the balloon site shown.
[0022] FIG. 1B shows a side view of an elastic sheath constructed
in accordance with the present invention, with the placement site
of the balloon within the central portion of the elastic tube. When
this embodiment of the elastic sheath is utilized, two conical cage
structures can be formed when the underlying balloon is expanded at
the balloon site shown.
[0023] FIGS. 2A-2C show side views of a rod constructed in
accordance with the present invention, with a balloon disposed
along the length of the rod and constraining material wrapped
around opposing segments of the balloon and adjacent segments of
the rod, leaving a segment of the balloon unwrapped and, hence,
capable of expansion. In FIG. 2A, the unconstrained portion of the
balloon is disposed toward the distal end of the rod. In FIG. 2B,
the unconstrained segment of the balloon is disposed toward the
central portion of the rod. In FIG. 2C, two unconstrained segments
of the balloon are disposed toward the central portion of the rod,
adjacent to one another.
[0024] FIGS. 3A-3C show side views of the rods shown in FIGS.
2A-2C, respectively, with the balloon expanded.
[0025] FIGS. 4A-4C show side views of devices of the subject
invention in an expanded configuration. FIG. 4A shows a device with
one balloon, in an expanded configuration, disposed toward the
distal end of the rod. FIG. 4B shows a device with one balloon, in
an expanded configuration, disposed toward the central portion of
the rod. FIG. 4C shows two balloons, in expanded configurations,
disposed toward the central portion of the rod.
[0026] FIG. 5 shows a side view of one embodiment of the device of
the invention, in an expanded configuration, with lateral bands
cross-linking the longitudinal bands, to produce a mesh.
[0027] FIG. 6 shows a plot (calibration curve) of balloon diameter
versus saline pressure. A control experiment with a bare balloon
was performed and compared with the device. As expected, higher
pressure was required to inflate the modified balloon in the
device.
[0028] FIGS. 7A and 7B show an in vitro human middle carotid artery
(MCA) model of the present invention, with A, B, C, D, and E
representing different locations of the MCA. FIG. 7A shows a
polypropylene tube of 2.5 mm inner diameter (ID). FIG. 7B shows a
clot holder that is a detachable silicone pouch with two openings.
The clot holder is attached to the polypropylene tube through
plastic fittings.
[0029] FIG. 8 shows angiography of a right kidney and renal artery
of a rabbit.
[0030] FIG. 9 shows angiography of the kidney shown in FIG. 8, with
successful thromboembolism evident.
[0031] FIG. 10 shows photographs of sliced 5 mm sections of
kidney.
[0032] FIG. 11 shows a side view photograph of a device constructed
in accordance with the present invention.
[0033] FIG. 12 shows a side view photograph of another embodiment
of the device constructed in accordance with the present invention,
with lateral bands cross-linking the longitudinal bands.
DETAILED DISCLOSURE OF THE INVENTION
[0034] The subject invention concerns a device and methods for
disrupting and/or removing occlusive material from lumens, such as
a blood vessel, ureter, urethra, fallopian tube, bile duct,
intestine, and the like. In addition to biological conduits, the
device and methods of the present invention can be utilized to
disrupt and/or remove occlusive materials from artificial conduits,
such as those constructed for insertion into the body (e.g.,
arterial or venous catheters). Where reference is made herein to
the "thrombectomy device" of the subject invention, it should be
understood that the device can be used to disrupt and/or remove
occlusive material from any lumen, biological or artificial.
[0035] The thrombectomy device 10 of the present invention has a
rod 24, an elastic sheath 40 that ensheaths at least one segment of
the rod 24, and means for radially expanding the elastic sheath 40
around the segment of the rod 24. Preferably, the expansion means
is at least one expandable balloon 30. In this embodiment, the
thrombectomy device 10 of the present invention comprises the rod
24, at least one expandable balloon 30 disposed along the length of
the rod 24, the elastic sheath 40 that covers at least a portion of
the expandable balloon 30 and ensheaths at least one segment of the
rod 24 adjacent to the balloon 30. Preferably, the rod 24, balloon
30, and elastic sheath 40, are co-axial.
[0036] Preferably, the means for expanding the elastic sheath 40
radially about the rod 24 is an expandable balloon 30. However,
other means for applying sustained radial pressure to the inner
surface of the elastic sheath 40, thereby expanding the elastic
sheath 40 radially about the rod 24, can be utilized. For example,
expansion means can include radially outwardly biased struts. In a
deactivated state, the biased struts can be retained within or
outside the rod 24. Upon activation, the struts are moved radially
outwardly against the inner surface of the elastic sheath 40,
thereby expanding the elastic sheath 40 and deploying the cage 50
(see, for example, U.S. Pat. No. 5,911,734, Tsugita et al., which
describes a filter and strut structure). In a further embodiment, a
compressive spring may be employed which pulls fore and aft ends of
expandable struts together, thereby expanding the elastic sheath
40. In other words, the elastic sheath 40 is spring activated.
Alternatively, the elastic sheath 40 can be expanded by a radially
expandable frame structure comprising frame struts (see, for
example, U.S. Pat. No. 6,277,139, Levinson et al., which describes
a frame structure attached to perforated filter material).
[0037] The elastic sheath 40 has a plurality of slits 20, with each
slit 20 separated from the adjacent slit 20 by a band 21 (or
string) of elastic material. The slits 20 can be on one side of the
expansion means, proximal or distal to the expansion means, or on
both sides of the expansion means, proximal and distal to the
expansion means. When the expansion means is activated to radially
expand the elastic sheath 40 about the rod 24, a portion of the
elastic sheath 40 will be displaced from a segment of the rod 24
that it previously ensheathed, the slits 20 expand, forming a
compartment 50 (also interchangeably referred to herein as the cage
50 or cage structure 50) around the rod 24. Thus, in embodiments
where an expandable balloon 30 is the expansion means, when the
balloon 30 is radially expanded about the rod 24 via internal
pressure, such as air pressure or saline pressure, portions of the
elastic sheath 40 that are adjacent to the balloon 30 are displaced
from the rod 24, and the slits 20 expand, forming a roughly
cone-shaped compartment 50 around the rod 24.
[0038] As used herein to describe the cage 50 of the subject
invention, the terms "cone-shaped", "conical", and "frustoconical"
are intended to include shapes that linearly, parabolically, or
hyperbolically taper from the expansion means (such as the balloon
30) down the length of the rod 24. Any expansion means that
radially expands the elastic sheath 40 to cooperate with the rod 24
in forming the cage 50 is sufficient. The conical body of the cage
50 extends (at its broadest point) expansion means to a proximal or
distal point (its narrowest point) on the rod 24, as shown in FIGS.
4A-4C and FIG. 5. Therefore, one end of the cage 50 is enlarged in
diameter when the expansion means is activated and the elastic
sheath 40 is displaced radially (outwardly from the rod 24), and
the other end of the cage 50 tapers to the rod 24, away from the
expansion means. In this way, in those embodiments wherein the
expansion means is one or more expandable balloons 30, the cage 50
of the thrombectomy device 10 is "balloon-activated".
[0039] When the expansion means is not activated, the elastic
sheath 40 (and, hence, the longitudinal bands 21) is in a position
of repose (collapsed) in which it is preferably substantially flush
with the rod 24. The conical cage 50 can be a unilateral cage,
forming on one side of the expansion means, or a bilateral cage,
forming on both sides of the expansion means. If the expansion
means is a continuously solid structure, such as an expandable
balloon 30, the bilateral cages will be separated by the expansion
means. However, the expansion means can be a discontinuously solid
structure, having voids through which the cages would be in
communication.
[0040] The rod 24 of the device 10 is preferably highly flexible to
facilitate navigation through tortuous biological lumens. The rod
24 can be hollow or solid, and can be composed of one or more of a
variety of materials, such as melt-processable and/or
non-melt-processable fluoropolymers (e.g., perfluoroalkoxy (PFA);
fluorinated ethylene propylene (FEP); poly(tetrafluoroethylene)
(PTFE); tetrafluoroethylene (MFA); ethylene tetrafluoroethylene
(ETFE); poly(vinylidene fluoride) (PVDF); ethylene
chlorotrifluoroethylene (ECTFE); and
poly(tetrafluoroethylene-co-perpropylvinylether) (PTFE/PPVE));
polyurethane; polyethylene; nylon; PEBAX, polyvinylchloride (PVC);
thermoplastic elastomers; polyesters; and radio-opaque and
non-radio-opaque resin blends. If the rod 24 is composed of one or
more polymers, the rod 24 can optionally include one or more
fillers, such as barium sulfate (BaSO.sub.4), bismuth trioxide
(Bi.sub.2O.sub.3), bismuth subearbonate (Bi.sub.2CO.sub.3), and
tungsten (W). Optionally, the rod 24 can include braided wire for
enhanced torque capabilities, as long as the rod is sufficiently
flexible and kink-resistant for the particular application. Braid
wire density, which is described as picks per inch (PPI), i.e., the
number of wire crossovers per inch of rod, can be optimized by
those skilled in the art. The rod 24 can have any of a variety of
shapes in cross-section. Preferably, the rod 24 has a substantially
circular cross-section. The length and diameter of the rod 24 will
depend on the diameter of the lumen and the target site. For
example, the length of the rod 24 can be within the range of about
50 centimeters to about 300 centimeters for many applications, and
from about 2.5 F (french) to about 10 F in diameter. Preferably,
the length of the rod 24 is about 150 centimeters and the diameter
of the rod 24 is about 0.25 millimeters.
[0041] The elastic sheath 40 has the general shape of a tube, with
a first end 12 with an opening 16 and a second end 14 with an
opening 18. When the device 10 is assembled, the rod 24 runs
through the openings 16, 18 of the elastic sheath 40.
[0042] Preferably, the elastic sheath 40 is produced from an
extremely flexible, tear-resistant, biocompatible polymer tube,
which can be composed of any of a variety of commercially available
thermoplastic elastomers. For example, in order to produce the
elastic sheath 40, slits 20 can be made in polymer tubes composed
of any of a variety of materials, such as silicone, polyurethane,
silicone-polyurethane copolymer, styrene-ethylene-butylene-styrene
(copolymer), and other suitable elastomeric materials. The elastic
sheath 40 should be sufficiently flexible and resilient such that
when a radial force is applied outward from within the sheath 40
(e.g., by the expanding balloon 30), the elastic sheath 40 will
expand at the point the force is applied, but will have sufficient
memory to revert to its regular tubular shape when the force is
removed.
[0043] The elastic sheath 40 has a plurality of slits 20. The slits
20 can be uniformly spaced from one another or non-uniformly spaced
from one another. Preferably, the slits 20 are longitudinally
arranged around at least a portion of the circumference of the
elastic sheath 40, or around entire circumference of the elastic
sheath 40. However, the slits 20 can be arranged non-longitudinally
on the elastic sheath 40. For example, the slits 20 can be arranged
at a diagonal relative to the length of the sheath 40. The slits 20
are preferably substantially parallel to one another. In one
embodiment, the slits 20 are arranged transverse to the length of
the sheath 40. In another embodiment, the slits 20 are arranged
non-transverse to the length of the sheath 40.
[0044] In one embodiment, the elastic sheath 40 has within the
range of 2 to 12 slits 20 proximal to the expansion means. In
another embodiment, the elastic sheath 40 has within the range of 2
to 12 slits 20 distal to the expansion means. In another
embodiment, the elastic sheath 40 has within the range of 2 to 12
slits 20 both proximal and distal to the expansion means.
[0045] The elastic sheath 40 preferably has a length within the
range of about 5 millimeters and about 5 centimeters, and a
diameter within the range of about 1 millimeter and about 1
centimeter. Preferably, the elastic sheath 40 has a thickness
within the range of about 0.05 millimeters and about 2
millimeters.
[0046] FIG. 1A shows a side view of an elastic sheath 40
constructed in accordance with the present invention, with the
placement site 22 of the balloon 30 within the distal end of the
elastic sheath 40. When this embodiment of the elastic sheath 40 is
utilized, one conical cage structure 50 can be formed when the
underlying balloon 30 is activated at the balloon site 22 shown. In
FIG. 1A, the longitudinal slits 20 extend from an area of the
elastic sheath 40 in close proximity to the balloon 30 and the
first end 12 of the elastic sheath 40, to the second end 14 of the
elastic sheath 40, permitting formation of the conical cage 50 that
extends from the balloon 30 to the point where the longitudinal
slits 20 terminate. FIG. 1B shows a side view of an elastic sheath
40 with the placement site 22 of the balloon 30 within the central
portion of the elastic sheath 40. When this embodiment of the
elastic sheath 40 is utilized, two conical cage structures 50 can
be formed (proximal and distal to the balloon 30) when the
underlying balloon 30 is expanded at the balloon site 22 shown.
[0047] FIGS. 2A-2C show side views of a rod 24 constructed in
accordance with the present invention, with a balloon 30 disposed
along the length of the rod 24 and constraining material 28 wrapped
around opposing sides of the balloon 30 and adjacent segments of
the rod 24, leaving the unconstrained segment of the balloon 30
capable of expansion. In FIG. 2A, the unconstrained segment of the
balloon 30 is disposed toward the distal end 26 of the rod 24 and
toward the distal end of the elastic sheath 40. In FIG. 2B, the
unconstrained segment of the balloon 30 is disposed more toward the
central portion of the rod 24 (as compared to FIG. 2A) and
approximately in the center of the elastic sheath 40. In FIG. 2C,
two unconstrained segments of the balloon 30 are disposed toward
the central portion of the rod 24, adjacent to one another, and
approximately in the center of the elastic sheath 40. In an
alternative embodiment, instead of leaving two or more segments of
a single balloon unconstrained, two or more separate balloons 30
can be utilized.
[0048] FIGS. 3A-3C show side views of the rods shown in FIGS.
2A-2C, respectively, with the balloons 30 expanded. FIGS. 4A-4C
show three embodiments of the device 10 in an expanded
configuration (i.e., with the cage 50 deployed). As shown in FIG.
4A, the elastic sheath 40 can be placed on the rod 24 such that the
expandable balloon 30 is off center relative to the length of the
elastic sheath 40. In this way, the size of the expanded cage 50
can be varied. Further, as shown in FIG. 4B, the elastic sheath 40
can be placed on the rod 24 such that the expandable balloon 30 is
approximately in the center of the elastic sheath 40, which
provides two cages 50 when then the device 10 is in an expanded
configuration (the balloon 30 is expanded). FIG. 4C demonstrates
that the device 10 may comprise a balloon 30 with two or more
unconstrained segments (also shown in FIG. 2C, unexpanded and
without the elastic sheath 40; and in FIG. 3C, expanded and without
the elastic sheath 40). Alternatively, instead of leaving two or
more segments of a single balloon unconstrained, two or more
individual balloons 30 can be utilized.
[0049] FIG. 5 shows a side view of one embodiment of the device 10
of the invention, in an expanded configuration, with lateral bands
34 cross-linking the longitudinal bands 21 such that the expanded
cage 50 resembles a mesh. The lateral bands 34 can bridge
longitudinal bands 21 at any of a variety of acute, obtuse, or
right angles relative to the longitudinal bands 21 which they
interconnect. When the device 10 is operated, the lateral bands 34
function to shear the occlusive material and enhance the ability of
the cage 50 to retain disrupted occlusive debris. The lateral bands
34 can be formed integrally within the elastic sleeve 40, in a
similar fashion as the longitudinal bands 21. Alternatively, the
lateral bands 34 can be subsequently added and secured to the
longitudinal bands 21.
[0050] Preferably, the expandable balloon 30 is spherical or
substantially spherical such that, when the balloon 30 is expanded,
a "cage" is formed. However, the balloon 30 can be any shape which,
when expanded, also stretches and expands the longitudinal slits 20
and longitudinal bands 21, permitting sufficient disruption of
occlusive material and, preferably, capture by the cage 50. For
example, the expandable balloon 30 can be ring-shaped, permitting
blood flow through the hole of the ring. Preferably, the balloon 30
is disposed concentrically around a portion of the rod 24, as shown
in FIGS. 11 and 12, or at its distal end 26. When the device 10 is
in an expanded configuration, the balloon 30, cage 50, and the rod
24 define a holding compartment to collect and hold occlusive
debris material. The balloon 30 can be arranged on the rod 24 in
any of a variety of ways permitting expansion of the balloon 30 and
formation of the cage 50 defining the holding compartment,
including many balloon-catheter arrangements known in the art
(e.g., FOGARTY embolectomy catheter; SENTRY balloon catheter;
EQUINOX occlusion balloon system; U.S. Pat. Nos. 3,435,826;
5,824,037; 4,762,130; 5,250,029; 4,403,612; 3,467,101; 5,232,445;
4,919,651; 4,637,396). The balloon 30 can be mounted longitudinally
or transversally on the rod 24, for example. Appropriate means for
expanding the balloon 30, such as by applying internal pressure to
the balloon 30, can likewise be employed. For example, the rod 24
can include one or more openings along its length that are in fluid
communication with the interior of the balloon 30, permitting
passage of fluid (e.g., gas or liquid) between the interior of the
hollow rod 24 and the interior of the balloon 30, as described in
U.S. Pat. No. 3,435,826. The rod 24 of the device 10 can include
concentric or non-concentric interior lumens or an external tube
connecting the balloon 30 to an external source of pressurized
fluid. The expandable balloon 30 can be composed of any of a
variety of materials. Preferably, the balloon 30 is a biocompatible
elastic material, such as synthetic or natural rubber latex,
silicone, polyurethane, polyisoprene
styrene-ethylene-butylene-styrene block copolymer (SEBS), or other
suitable elastomeric material.
[0051] At least a portion of the balloon 30 can be radially
constrained, leaving at least one portion of the balloon 30
radially unconstrained. In this way, when pressure is applied to
the constrained balloon 30, the unconstrained portion or
unconstrained portions of the balloon 30 expand but the constrained
portion or portions do not. In one embodiment, an elongated,
tube-shaped balloon 30 is utilized (such as an angioplasty
balloon), wherein the balloon 30 is radially constrained at either
or both ends, leaving one or more segments of the balloon 30
unconstrained. In this way, when pressure is applied to the
constrained balloon 30, the unconstrained segment or unconstrained
segments of the balloon 30 preferably expand to form a sphere or
substantially spheroid shape. The radial constraint can be provided
in any of a number of ways. For example, radial constraint can be
provided by a constraining material 28 that surrounds and radially
constrains portions of the balloon 30 (e.g., segments of the
balloon 30 at either or both ends). The constraining material 28
prevents those portions of the balloon 30 that the constraining
material 28 surrounds from expanding, leaving the rest of the
balloon 30 (e.g., the center portion of the balloon 30) capable of
full expansion. For example, the constraining material 28 can be a
fiber, such as polyurethane fiber (e.g., SPANDEX), that is wrapped
around those portions of the balloon 30 to be constrained.
[0052] When the balloon 30 is expanded, the balloon 30 preferably
has a diameter within the range of about 1 millimeter to about 3
centimeters, and a length within the range of about 1 millimeter to
about 1 centimeter. Preferably, the thickness of the balloon 30 is
within the range of about 0.01 millimeter and about 0.5
millimeter.
[0053] The thrombectomy device 10 of the present invention is
particularly useful for treating vascular thrombosis and
pathological conditions associated with vascular thrombosis, such
as ischemic thromboembolic stroke. Because the device 10 of the
subject invention can be constructed so as to be highly flexible
and maneuverable, the device 10 will be suitable for operation in
previously inaccessible anatomical regions, such as intracranial,
urinary, biliary, bronchial, coronary, or other physiological lumen
systems. Due to its elastic property, the cage 50 can be expanded
and contracted multiple times to obtain optimal size and position
before it is used to retrieve occlusive debris. Because of the
soft, elastic property of the longitudinal bands 21 of the sheath
40, the device 10 will cause minimal trauma to the endothelial
cellular layer. Advantageously, the size of the cage can be
controlled. The cage is formed only when the balloon is deployed by
pressure. The higher the pressure applied to the balloon, the
larger the cage's size. In addition, it will be possible to work
with a variety of lumen sizes with the same device.
[0054] In another aspect, the subject invention pertains to a
method for disrupting and/or removing occlusive material from a
biological lumen, such as a blood vessel. The for sake of
simplicity, the method will be described wherein the expansion
means is an expandable balloon 30. However, other means for
expanding the elastic sheath 40 to form the cage 50 can be
utilized. The method is carried out by inserting the device 10 of
the invention into the lumen, placing the expandable balloon 30 and
cage 50 at a target site within or adjacent to the occlusion,
expanding the balloon 30, and operating the device in a
back-and-forth and, optionally, twisting motion such that the
occlusion is mechanically disrupted by shearing contact with the
longitudinal bands 21 of the elastic sheath 40, or with the
longitudinal bands 21 and lateral bands 34, depending upon the
particular embodiment. Advantageously, occlusive fragments and
debris material produced by expansion of the balloon 30 against the
occlusion and/or shearing contact of the occlusion with the bands
21, pass through the expanded slits 20, and are thereby captured
within the cage formed by the expanded elastic sheath 40.
Advantageously, although the longitudinal bands 21 of the device 10
may contact the luminal wall, little or no damage to the luminal
wall results. Optionally, the balloon 30 can then be partially or
entirely deflated, in order to narrow or close the slits 20,
thereby more securely containing the disrupted occlusive debris
material between the bands 21 of the elastic sheath 40, the balloon
30, and the rod 24. The device 10 is then removed from the
patient.
[0055] For example, an incision can be made and the device 10 of
the subject invention can be inserted through an artery, such as
the femoral artery in the patient's groin, and directed to the site
of the occlusion. The device 10 can be inserted and positioned at a
point in the lumen before, within, or beyond the occlusion. Either
end of the device 10 can be inserted first into the lumen, so long
as the longitudinal bands 21 and/or lateral bands 34 can make
searing contact with the occlusion, thereby disrupting the
occlusion and, optionally, providing an opportunity for the
expanded cage 50 to capture particles from the disrupted
occlusion.
[0056] Once the device 10 is in place, the means for expanding the
balloon 30 can be activated. For example, the device 10 can be in
operable communication with a pump that provides gas or fluid
(e.g., saline solution) to the balloon 30. The balloon 30 can be
expanded to such an extent that the balloon 30 makes radial contact
with the inner walls of the lumen or occlusive material deposited
on the luminal walls. Optionally, the balloon 30 can be expanded to
such an extent that the lumen becomes dilated, as during
angioplasty procedures. Physicians of ordinary skill in the art can
determine optimal pressures to be applied to the balloon 30,
optimal diameters to which the balloon 30 is to be expanded within
the occluded lumen, and durations of balloon 30 expansion. The
operator of the device 10 can use a back-and-forth and/or twisting
motion in order to facilitate disruption and capture of the
occlusive material within the cage 50. The balloon 30 can then be
deflated, contracting the cage 50, and the device 10 can be
withdrawn from the biological lumen. Preferably, the device 10 is
operated such that any occlusive debris freed by the device is
maintained proximally of the balloon 30 and the distal rod end 26,
thereby minimizing the risk of occlusive debris migrating to a
remote site.
[0057] Optionally, the thrombolytic device 10 of the subject
invention can be used in conjunction with various pharmacologic
substances that breakup or dissolve the occlusion, and/or prevent
the formation of future occlusions. For example, in the case of
blood clots (also known as thrombi), various anticoagulant,
thrombolytic (so called "clot-busting" drugs) or anti-platelet
agents can be administered orally or intravenously. Examples
include heparin (CALCIPARINE, HEPATHROM, LIP-HEPIN, LIQUAEMIN,
PANHEPRIN), warfarin (ATHROBMIN-K, PANWARFIN), tissue plasminogen
activator (tPA; ALTEPLASE; ACTIVASE), streptokinase (KABIKINASE,
STREPTASE), urokinase (ABBOKINASE), anistreplace, aminocaproic
acid, aprotinin, acetylsalicylic acid (aspirin), dipyridamole
(PERSANTINE), abciximab (CENTOCOR), dalteparin (FRAGMIN),
enoxaparin (LOVENOX), hirudin (DESIRUDIN), 4-hydroxycoumarin
(COUMADIN), lepirudin (REFLUDAN), protamine sulfate, phytonadione
(Vitamin K.sub.1), reteplase (RETAVASE), and ticlopidine (TICLID).
Many of these agents operate by inhibiting the clotting mechanism
(anticoagulants), lysing thrombi (fibrinolytic agents), and
interfering with platelet adhesion and/or aggregation.
[0058] Various components of the thrombolytic device 10, such as
the rod 24, the elastic sheath 40, and/or the expansion means (such
as the expandable balloon 30), can be impregnated or coated with
one or more biologically active agents, such as pharmacologic
substances that breakup or dissolve the particular occlusion to be
removed. The biologically active agents can function on contact
with the device 10 or the substances can be released from the
device 10 into the biological lumen in a controlled release
fashion. Optionally, the biologically active agents can be released
and/or become activated upon contact with blood, or otherwise be
responsive to the physiological environment. For example, the
biologically active agents can be temperature-sensitive and/or
pH-sensitive. As an alternative to impregnated or coated
components, the biologically active agent can be delivered by other
means, such as a port on the rod 24 of the device 10 that permits
injection of the biologically active agent at a target site. As
used herein, the term "biologically active agent" refers to any
substance that is capable of promoting or causing a therapeutic
effect in a patient.
[0059] Methods known in the art for insertion and operation of an
angioplasty catheter can also be utilized with the device 10 of the
present invention. For example, the device 10 of the present
invention can be introduced into a biological lumen through an
introducer (also known as an introducing catheter), which is used
to access the lumen. Guide wires can also be utilized.
[0060] As indicated above, where reference is made herein to the
"thrombectomy device" or "thrombolytic device" of the subject
invention, it should be understood that these terms are used herein
interchangeably and the device can be used to disrupt and/or remove
any occlusive material from any lumen, whether the occlusive
material and lumen are biological or artificial. For example, in
addition to disrupting and, optionally, removing thrombus or other
endogenous embolic material, such as calcifications, cholesterol,
plaque, etc., from a biological lumen, the device 10 of the present
invention can be used to disrupt and/or remove exogenous embolic
material, such as embolic agents. Embolic agents that can be
disrupted and/or removed with the device 10 of the present
invention include, but are not limited to, adhesive (such as
polymerizing adhesive), gel, silicone rubbers, urethanes and other
organic elastomers, polymerizable protein solutions, silk sutures,
polyvinyl alcohol (PVA) particles, cross-linked polyvinyl alcohol
foam, polyurethane foam, acrylic polymers, polyethylene foam,
silicone foam, fluorinated polyolefin foam, and/or an
ethylene-vinyl-alcohol copolymer commercially available under the
designation ONYX by MICRO THERAPEUTICS, INC (Irving, Calif.)
(Dehdashti, A. R. et al., Neurosurg. Focus 11(5):1-6, 2001; Halbach
V. V. et al., AJR 153:467-476, 1989; Purdy P. D. et al., J.
Neurosurg. 77:217-222, 1992; Purdy P. D. et al., Am. J.
Neuroradiol. 11:501-510, 1990).
[0061] ONYX is a liquid embolic (or embolization) agent that is a
mixture of ethylene-vinyl alcohol copolymer (EVOH), dimethyl
sulfoxide (DMSO), and micronized tantalum (to enable visualization
under fluoroscopy) that can be used to fill aneurysms. Contact of
ONYX with blood results in its solidification from the outside
inward, thereby forming a spongy polymeric cast (Jahan R. et al.,
Neurosurgery 48(5):984-997, 2001; Hamada J. et al., J. Neurosurg.
97(4):889-895, 2002; Hamada J. et al., Am. J. Neuroradiol.
17(10):1895-1899, 1996). The ONYX embolic agent can be used for the
treatment of aneurysms and arterio-venous malformations (AVMs), two
conditions which can lead to hemorrhagic stroke. Once delivered
inside the targeted malformation, the ONYX embolic agent quickly
solidifies into a spongy polymer mass designed to seal off the
defective portion of the vessel. In aneurysm and AVM applications,
the ONYX filling is intended to reduce the risk of rupture and
subsequent stroke. The device 10 of the present invention can be
used to disrupt and/or remove excess or otherwise undesired ONYX
material present within a vessel.
[0062] Depending upon the occlusive material to be removed or
retrieved, disruption or breaking apart of the occlusive material
may not be necessary. For example, where the device 10 of the
present invention is used to retrieve embolization devices, such as
those used in the field of cardiology for treating aneurysms, no
disruption of the embolization device may be necessary and the
embolization device may simply be captured with the cage 50 of the
device 10 of the present invention and pulled out of the biological
lumen. Examples of such embolization devices include, but are not
limited to, PVA particles, detachable balloons, and embolization
coils. Advantageously, large or small amounts of occlusive material
can be removed using the device 10 of the present invention. The
occlusive material can be any occlusive or potentially occlusive
material that can be dislodged from the luminal wall and/or
captured by the cage 50 of the device 10. The occlusive material
can be of various phases, such as solid, semi-solid, or liquid.
[0063] Optionally, any component of the thrombectomy device 10 of
the subject invention can be at least partially composed of an
imageable material. For example, the rod 24, balloon 30, and/or
elastic sheath 40, can be composed of an imageable material. As
used herein, an "imageable material" includes those materials the
location of which can be discerned within a given opaque, ambient
medium such as biological tissue, using the appropriate sensing
equipment, such as imaging equipment. The imageable material
selected should have an image "signature" discernibly different
from that of the surrounding medium into which the device 10 is to
be introduced. Components of the device 10 can be coated or
impregnated with one or more imageable materials, for example.
[0064] In one embodiment, the imageable material is an echogenic
material with an acoustic impedance different from that of the
surrounding medium (i.e., high acoustic impedance differential),
enabling the thrombectomy device 10 to be imaged using a sonic
imaging device (e.g., ultrasound imaging equipment). A variety of
materials that are echogenic (i.e., sound reflective) can be
utilized, such as aluminum, hard plastic, sand, and metal
particles. For example, the echogenic material can be any of those
materials described in U.S. Pat. No. 5,201,314 and U.S. Pat. No.
6,106,473, or a combination of those materials. In another
embodiment, the imageable material is a radio-opaque material (such
as barium sulfate, tantalum, and/or gadolinium particles) that can
be imaged with radiographic equipment (e.g., an x-ray machine or
computed tomography (CT) scanner). In a further embodiment, the
imageable material is a substance that can be imaged using magnetic
resonance imaging/spectroscopy (MRI/MRS) equipment. Other imageable
materials include those materials detectable through single photon
emission tomography (SPECT) or positron emission tomography (PET),
for example. The component or components of the thrombectomy device
10 can be wholly or partly composed of the imageable material. As
indicated above, the imageable material can be in the form of a
coating or film on an underlying substrate.
[0065] Contrast media, such as dyes, can also be used in
conjunction with the appropriate imaging equipment in order to
discern more details within the biological lumen. For example,
barium-containing and iodine-containing dyes can be administered in
conjunction with x-ray or CT imaging. Gadolinium, for example, can
be used in conjunction with MRI imaging.
[0066] Optionally, the device 10 of the present invention can
further include a means for providing a jet or jets of fluid under
pressure to the distal end 26 of the rod 24, and/or at any point or
points along the rod's length. For example, the rod 24 of the
device 10 can be hollow and in operable communication with a pump
that provides fluid under pressure to the distal end of the rod 24,
where it exits the rod 24 through an outlet. The fluid jet can
facilitate disruption of occlusions within the biological
lumen.
[0067] Optionally, the device 10 of the present invention can
include a means for vacuuming occluding debris from the lumen at
the distal end 26 of the rod 24, and/or at any point or points
along the rod's length. For example, the rod 24 of the device 10
can be hollow and in operable communication with a means for
providing negative pressure to the interior of the rod, such that
occlusive debris is drawn into inlets along the length and/or the
end of the rod 24. Optionally, the device 10 can include both a jet
means and a vacuum means, as described above. In one embodiment,
the jet means and vacuum means can be alternatively operated to
expel fluid from the device 10, in order to disrupt an occlusion,
and to take up the occlusive debris upon activation of the vacuum
means.
[0068] In addition to natural biological conduits of the body, such
as blood vessels (veins, arteries, etc.), ureter, urethra,
fallopian tube, bile duct, intestine, and the like, the device 10
and methods of the present invention can be utilized to remove
occlusive materials from other biological or artificial conduits,
such as arterial or venous catheters, stents, grafts, such as
peripheral femoral-popliteal, coronary bypass grafts and dialysis
access grafts, and fistulas.
[0069] The occlusion-removing device 10 of the present invention
can be utilized to disrupt and/or remove occlusive material from
natural or artificial lumens within humans or animals, such as
non-human mammals. Thus, the device 10 of the present invention can
be used in a variety of veterinary applications in order to treat
domesticated or non-domesticated animals. The dimensions of the
various components of the device 10 can be optimized for the
particular animal subject.
[0070] In another aspect, the present invention concerns a device
60 useful as an in vitro model of luminal occlusion, such as that
shown in FIGS. 7A and 7B, and methods for using the device 60 to
test the efficacy of devices and methods for treating luminal
occlusions. The device 60 includes a flexible hollow tube 61 having
a first end 62 and second end 64. The flexible tube 61 can be
composed of any material, such as silicone, which permits bending
of the tube 61 into a tortuous shape, if desired. For example, the
flexible tube can be composed of one or more melt-processable or
non-melt-processable polymers; polyurethane; polyethylene; nylon;
PEBAX, polyvinylchloride (PVC); thermoplastic elastomers;
polyesters; and resin blends.
[0071] As shown in FIG. 7A, one or more bends can be placed in the
tube 61 in order to simulate vasculature of the brain, for example.
At one or more points along the length of the tube 61, occlusion
sites can be established. In one embodiment, each occlusion site
(A, B, C, D, E) has a three-way receptacle 66 (also referred to
herein as a "clot holder") with ports 68 (also referred to herein
as "fittings") connecting the receptacle 66 to the tube 61. The
three-way receptacle 66 contains an occlusion 70, such as a
naturally occurring or artificial clot. The receptacle 66 can her
include an access port 73 for inserting an occlusion 70. The
diameter and length of the tube 61 are preferably of dimensions to
accommodate a particular test device to be inserted into the first
or second ends 62, 64 of the tube 61 and to mimic the particular
artificial or biological lumen to be modeled. Optionally, the tube
61 can have one or more branches and sub-branches. The tube 61 can
contain a fluid, such as saline or blood, to mimic a biological
vessel. The test device can be inserted into either end of the tube
61 and navigated to an occlusion site to act on an occlusion 70.
The performance of the test device can then be evaluated. Test
criteria will depend upon the nature of the technique and/or test
device and the objective to be achieved.
[0072] The terms "comprising", "consisting of" and "consisting
essentially of" are defined according to their standard meaning.
The terms may be substituted for one another throughout the instant
application in order to attach the specific meaning associated with
each term.
[0073] As used in this specification and the appended claims, the
singular forms "a", "an", and "the" include plural reference unless
the context clearly dictates otherwise. Thus, for example, a
reference to "an expandable balloon" includes more than one such
balloon. A reference to "an elastic sheath" includes more than one
such sheath. A reference to "a compartment" (i.e., "a cage")
includes more than one such compartment. A reference to "an
occlusion site" includes more than one such occlusion site, and the
like.
[0074] All patents, patent applications, provisional applications,
and publications referred to or cited herein, whether supra or
infra, are incorporated herein by reference in their entirety to
the extent they are not inconsistent with the explicit teachings of
this specification.
[0075] Following are examples which illustrate procedures,
including the best mode, for practicing the subject invention.
These examples should not be construed as limiting. All percentages
are by weight and all solvent mixture proportions are by volume
unless otherwise noted.
Example 1
Construction of a Thrombectomy Device
[0076] A thrombectomy device of the subject invention has been made
in a modular fashion. The device consists of an elastomeric polymer
tube of an appropriate size and a balloon catheter.
[0077] Tubes were made from CARBOSIL 40 90A (The Polymer Technology
Group, Inc., Berkeley, Calif.), a solution grade elastomeric,
tear-resistant silicone-polyurethane thermoplastic copolymer, by
the dip-coating method. Several 21 (0.80 mm outer diameter, OD)
gauge injection needles (MONOJECT from Sherwood Medical, St. Louis,
Mo.) were used as mold substrates. Each needle was 1.5 inches long
and the size (OD) of the needle represents approximately the inner
diameter (ID) of the resulting tube. Two times dipping of each
needle in 15 wt % polymer solution in tetrahydrofuran (THF) at
about a 4 mm/sec withdrawal rate and a 30 minute interval between
two successive dippings formed an approximately 90 .mu.m thick
polymer coating. Coated needles were then vacuum-dried. Coating on
both ends of the needle was non-uniform. Therefore, keeping a
uniform section of 30 mm long coating around the middle of the
needle, the remaining coating was carefully cut by a sharp surgical
razor blade (MILTEX Surgical Blades, model 4197 #11, MILTEX
Instrument Company, Inc., Bethpage, N.Y.) and then removed. At this
point, the coating could be detached in the form of a uniform
tube.
[0078] Without detaching the coating from the needles, a pattern
was made on the coating manually by a sharp black permanent marker,
as shown in FIGS. 1A and 1B, (SHARPIE Ultra Fine Point Permanent
Marker from SANFORD Corporation, Bellwood, Ill.). The pattern was
along the length and around the needle. A total of 5 slits 20 were
then cut along the pattern with a stainless steel surgical blade of
about 10 .mu.m tip size. Slits 20 were 10 mm long and the spacing
between two slits 20 (defining a band 21 there between) was about
550 .mu.m. This step was carried out under a microscope. Needles
were then immersed in 60% acetone in water (V/V) for 5 minutes for
swelling the polymer. The coating was then detached in the form of
a uniform tube when pushed lightly off the needle. The actual
modified polymer tube is shown in FIG. 11.
[0079] A SENTRY balloon catheter was purchased from BOSTON
SCIENTIFIC-TARGET, Fremont, Calif. The balloon diameter and the
balloon length were 3.5 mm and 10 mm when inflated. The balloon
portion of the catheter was modified by constraining more of the
proximal end of the balloon than the distal end, as shown in FIG.
2A, or by constraining about equal portions of the proximal end and
distal end of the balloon, as shown in FIGS. 2B and 2C. The
modified balloon portion was 2 mm long. This was done by wrapping
around a stretchable, segmented polyurethane fiber (The Polymer
Technology Group Inc., Berkeley, Calif.). Prior to wrapping, the
fiber was pre-stretched to about 100% of its original length. When
pressure was applied by injecting saline solution, only the
unconstrained segment of the balloon 30 inflated, as shown in FIGS.
3A-3C.
[0080] The modified polymer tube was then swelled by immersion in
60% acetone in water (V/V) for 5 minutes. Swelling of approximately
40% of its original size occurred. The swelled tube was then
slipped over the modified balloon in a desired location. The ID of
the tube was smaller (about 0.2 mm) than the OD of the balloon.
Once dried under the vacuum, the elastomeric tube captured the
modified balloon firmly, as shown in FIGS. 4A-4C, with the actual
device shown in FIG. 11.
[0081] Two preliminary tests were performed on the thrombectomy
device: mechanical testing and in vitro performance testing.
Example 2
Mechanical Testing of a Modified Balloon Under Applied Saline
Pressure
[0082] To determine the inflated balloon size with respect to the
applied saline pressure, the device was installed on a
micromanipulator. Using a digital inflation device and fluid
dispensing syringe (MONARCH 25, MERIT MEDICAL SYSTEMS, Inc., South
Jordan, Utah) the saline pressure was applied. The micromanipulator
read the inflated balloon diameter quite accurately at different
saline pressures. The digital inflation device showed the applied
saline pressure directly. A plot (calibration curve) of balloon
diameter versus saline pressure was constructed as shown in FIG. 6.
A control experiment with a bare balloon was performed and compared
with the device. As expected, higher pressure was required to
inflate the modified balloon in the device. This type of
calibration curve will be helpful for both in vitro and in vivo
device operation.
Example 3
In Vitro Performance Testing of the Thrombectomy Device in Silicone
Tubing
[0083] 40 cm long silicone tubing (ID 2.5 mm) was selected for the
preliminary in vitro performance testing of the device 60. Two
syringes were placed at both ends of the tube 61. Due to the
flexible nature of the tube 61, an approximately tortuous shape
could be given without kinking, as shown in FIG. 7A. Rabbit blood
clots were used as models for the experiment. 1 ml of blood was
allowed to coagulate in a 7 ml sterile blood collection tube for a
period of 1 hour. The tube 61 was then opened and the bulk clot was
removed and cut in half. Each section was weighed and recorded. The
silicone tube 61 was prepared by flushing it with saline solution
to remove any air bubbles from the tube 61. The blood clot was
placed in a 3 ml syringe and injected into the silicone tube 61.
Saline was then injected into the silicone tube 61 until the clot
reached approximately 20 cm from the proximal end (first end, 62)
of the tube 61. The syringe on the distal end (second end, 64) was
kept attached to the silicone tube 61, but the proximal syringe was
replaced with a 3-way device that allowed the catheter to be
inserted.
[0084] The thrombectomy device 10 was first navigated through the
tube 61 and passed through the emboli. The thrombectomy device 10
was then slowly deployed up to a desired size (about 2.2 mm) and
pulled back. The cage structure was able to grab the emboli and
move it out of the tube 61.
Example 4
Materials for Making the Elastic Sheath
[0085] This component is the most important part of the
thrombectomy device because it will directly contact and manipulate
the thrombus. A modified balloon catheter will assist this
component to make its cage-like shape when deployed.
[0086] Tear-resistant biocompatible elastomeric polymer materials
will be chosen for making tubes. Two types of commercially
available solution grade (SG) thermoplastic materials will be
selected: a polyurethane (TECOFLEX SG-80A, THERMEDICS Polymer
Products, Woburn, Mass.); and a few silicone-polyurethane
copolymers (CARBOSIL 40 90A, PurSil 20 80A and PurSil AL5 75A, The
Polymer Technology Group Inc., Berkeley, Calif.). TECOFLEX SG-80A
is an aliphatic polyether-based thermoplastic polyurethane (TPU).
PURSIL silicone-polyether-urethane and CARBOSIL
silicone-polycarbonate-urethane are thermoplastic copolymers
containing silicone in the soft segment. PURSIL 20 80A is an
aromatic silicone polyetherurethane whereas PURSIL AL5 75A is an
aliphatic silicone polyetherurethane. Table 1 lists some of the
physical test data of these materials reported by the
manufacturers. From the table it is clear that these materials
cover a range of mechanical properties. The purpose of selecting
all four materials under this study is to find the right material
for the optimized device.
TABLE-US-00001 TABLE 1 Physical Test Data of Elastomeric Polymer
Materials Tensile Stress Tensile Stress at 100% at 300% Ultimate
Ultimate Elongation Elongation Tensile Elongation Tear Strength,
Elastomer (psi) (psi) Strength (psi) (%) die "C" (pli) TECOFLEX 300
800 5800 660 N/A EG-80A PURSIL 20 270 570 5300 900 390 80A PURSIL
900 1630 4900 770 115 AL5 75A CARBOSIL40 1310 2400 4300 530 500
90A
[0087] The data for TECOFLEX EG-80A represent data for extrusion
grade materials. The solution grade data are not available. The
solution grades differ from the extrusion grades in that they
contain no melt processing lubricants.
[0088] If required, in order to clearly visualize the tube under a
fluoroscope while performing in vivo tests, the tube can be
constructed so as to be radio-opaque. Radio-opaque grade TECOFLEX
is available with 20 wt % and 40 wt % loading of barium sulfate.
Other polymers could be either blended with barium sulfate or could
be custom-blended from the manufacturer.
[0089] The dip-coating method will be used to make polymer tubes.
TECOFLEX EG-80A is soluble in N,N-dimethylacetamide (DMAC), and
other silicone-polyurethane copolymers are soluble in
tetrahydrofuran (THF). Tubes will be made using 21 gauge needles
(OD 0.8 mm). The inner diameter (ID) of the tube will be 0.8 mm or
little less, if the polymer shrinks after drying. Tube thickness
generally depends upon three parameters: the polymer concentration;
the total number of dippings; and the withdrawal rate. By proper
adjustment of these three parameters, tubes will be made of about
100 .mu.m in thickness. Table 2 shows the details.
TABLE-US-00002 TABLE 2 Elastic Sheath Design Calculated spacing
between Needle Tube thickness two adjacent size Number Slit length
(mm) (.mu.m) slits (.mu.m) (gauge) of slits Pattern (approximately)
(approximately) (approximately) 21 (0.8 mm 5 A 10 (type 1A) and 100
630 OD) 15 (type 2A) B 6.5 (type B)
[0090] Tubes will be modified in three different patterns (A, B,
and C), as shown in FIGS. 2A-2C, respectively, to produce elastic
sheaths 40 of the subject invention. Patterns A and B will produce
sheaths 40 with 10 mm and 15 mm long slits 20, respectively. In
structure A, the modified balloon 30 will be located at one end of
the slits 20 (towards the catheter tip); whereas, in structure B,
the balloon 30 will be located in the middle along the length of
the slits 20. The operation of the device with structure A is "one
way" such that, after being passed through the thrombus, the cage
structure is deployed and then pulled back through the thrombus,
disrupting the thrombus and capturing thrombotic debris. Unlike
structure A, structures B and C have double cage structures, which
means that they function to disrupt and capture thrombus both when
pushed and pulled through the occluded region of the vessel.
Therefore, it is expected that the double cage structure will have
an advantage in grabbing more thrombus, compared to the single cage
structure. As described previously, longitudinal slits 20 will be
made under a microscope using sharp surgical blade of about 10
micron tip size. The total number of longitudinal slits 20 in each
elastic sheath 40 will be 5.
Example 5
Mechanical Testing of an Elastic Sheath
[0091] All mechanical testing will be performed using an INSTRON
model 4301 (INSTRON Corporation, Canton, Mass.). Using an
appropriate load cell (e.g., tension/compression 250 gm load cell,
INSTRON model: type 00), a complete stress-strain profile for both
modified and unmodified tubing will be generated. By this
measurement, the mechanical characteristics of all three
structures, A, B and C, will be compared directly.
[0092] Flexibility and maneuverability testing are useful to
predict the feasibility of navigating the device through the
tortuous intracranial vasculature system in the brain. A
three-point bend test will be conducted. A bend test fixture and an
"S" hook for the bend test will be designed and constructed. Thin
tubes will likely kink while performing the bend test. In order to
overcome this problem, compliant (highly flexible) silicone rods of
an appropriate size will be made and used as substrate for the
tube. Once the tube is mounted over the rod, it will not kink while
performing the bend test. Approximately 0.8 mm OD silicone rods
will be made from two-component platinum cure SILASTIC T2 (DOW
CORNING, Midland, Mich.) mold making rubber. Appropriately sized
(e.g., about 0.8 mm ID) melting point glass capillary tubes
(KIMAX-51 borosilicate glass from KIMBLE-KONTES, Vineland, N.J.)
will be used as a mold substrate. Once cured inside the capillary
tube, the silicone rods will be removed from the mold by dissolving
the glass in hydrofluoric acid.
[0093] The measurement of the string tear strength will be
important in order to prevent breaking of the strings in the cage
structure during the thrombus retrieval process. We will first
mount the modified tube on an appropriate rigid rod (stainless
steel needle), and then both ends of the tube will be fixed to the
rod by tying with non-stretchable fiber. Using an INSTRON setup,
each string will be pulled with respect to the rest until it
breaks. A stress versus displacement plot will be generated for the
comparison of string strengths of three different structures.
Example 6
In Vitro Performance Testing of the Thrombectomy Device in a Middle
Carotid Artery (MCA) Model
[0094] SENTRY balloon catheters (150 cm long) will be purchased
from BOSTON SCIENTIFIC-TARGET, Fremont, Calif. The balloon diameter
and the balloon length are 3.5 mm and 15 mm, respectively, when
inflated. The diameter of the catheter at the balloon is 0.86 mm
when un-inflated. The balloon portion of the catheter will be
modified to create balloon types A and B by constraining it at both
ends into a 2 mm long balloon in the middle, as shown in FIGS. 2A
and 2B. Balloon type C (FIG. 2C) will be made similarly as type A
and B with the exception that, in type C, the balloon will be
further split into two halves by constraining the middle portion of
the balloon. This will be done by wrapping around stretchable,
segmented polyurethane fiber. Prior to wrapping, the fiber will be
pre-stretched about 100% of its original length. The balloon
modification steps will be carried out under a microscope. When
pressure is applied by injecting saline, only the unobstructed
balloon portion will inflate, as shown in FIGS. 3A-3C. Mechanical
testing of the modified balloon catheter will involve measurement
of the balloon diameter increase with respect to the saline
pressure to determine the optimum inflation pressure. Mechanical
testing on these modified balloons will then be performed. A plot
will be constructed showing the increase of the balloon diameter
with respect to the increase of the saline pressure. This plot will
facilitate the determination of optimum saline pressures for a
desired balloon size.
[0095] Both the modified balloon catheter and the modified tube
will be re-inspected under a microscope before the final
assembling. The modified polymer tube will then be swelled by
immersing it in an appropriate solvent as described before.
Swelling of approximately 30% of its original size would be
sufficient to slip it over the modified balloon. The ID of the tube
will purposely be made smaller than the OD of the balloon portion
of the catheter. Once dried under the vacuum, the elastomeric
tubing will capture the modified balloon firmly. Schematic
representation of the device is shown in FIGS. 4A-4C. In order to
secure the thrombus inside the cage structure, a "spider-web" like
pattern can be made near the balloon of the device, covering about
50% of the tube length, for example, as shown in FIG. 5. Polymer
solution (same as the tube material) will be directly applied in
the form of a fine fiber onto the inflated device in such a way
that it will connect the elastomeric strings.
[0096] The mechanical testing will be performed using an Instron
setup as described earlier in the preliminary study section. The
flexibility testing of the device will be performed by a three
point bend test. A calibration curve will be generated showing
maximum cage diameter with respect to the saline pressure. This
experiment will help for in vitro and in vivo testing of the
device.
[0097] A polypropylene tube (PP) of 2.50 mm ID will be used for
making the model of the tortuous MCA. This type of tube may kink
while bending it to give the tortuous shape. To overcome this
problem, an appropriate size copper wire will be inserted inside
the PP tube first to give the right shape to the tube. Translucent
silicone glue (SILASTIC T2 from DOW CORNING) will be applied over
the PP tube and then it will be heat treated. Once cured, silicone
oil will be injected into the tube to make the tube interior
slippery. Then the structure will be straightened and the copper
wire support will be removed. Once released, the tube will return
to its tortuous shape. Silicone over-coating should reinforce and
retain the structure. It will then be cleaned and installed as
shown in FIG. 7A.
[0098] Clots will be made directly from rabbit blood. The plastic
MCA model will be marked A, B, C, D and E, as shown in FIG. 7A,
which will represent different locations of the MCA. The tube will
then be cut at each location to attach a clot holder. The clot
holder will be a detachable silicone pouch with two openings, as
shown in FIG. 7B. Both openings of the holder will be attached to
the model through plastic fittings. This pouch will then be filled
with condensed clot (the clot condensation will be done by
centrifugation). Before operation of the device, the model will be
bathed with saline solution. All locations, from A through E, will
be tested with the device to evaluate the device performance at
each location. The feedback from the in vitro testing will help for
the further development of the device. A repeated redesigning and
remanufacturing process will be carried out to optimize the device
performance for three different cage patterns (A, B and C). This
investigation will provide information on the best polymer material
(out of four different materials) for each cage pattern.
Example 7
In Vivo Performance Testing of the Thrombectomy Device in a Rabbit
Kidney Occlusion Model
[0099] A rabbit kidney occlusion model closely mimics the MCA in
humans (in terms of the lumen size) will be utilized. Prior to the
surgical procedure, the animal will be sedated with acetylpromazine
(0.5-2.0 mg/kg SQ or IM) and 0.5 ml of blood will be drawn from the
central auricular artery and allowed to coagulate in a 3 ml blood
collection tube with a wire for one hour at 37.degree. C. This
autologous thrombus will be used for creation of the thromboembolic
occlusion. The animal will then be weighed to determine proper
injectable anesthetic doses, and placed under general anesthesia.
General anesthesia will be induced with KAX (0.6 ml/kg), a mixture
of 10 ml ketamine HCl (PHOENIX PHARMACEUTICALS, 100 mg/kg), 2.0 ml
acepromazine maleate (PHOENIX PHARMACEUTICALS, 10 mg/kg), and 1.5
ml xylazine (PHOENIX PHARMACEUTICALS, 100 mg/kg).
[0100] Following sufficient sedation, the animal will be intubated
and attached to a ventilator providing an oxygen mixture (21%
oxygen USP, 79% nitrogen). The surgical site will then be shaved,
prepped and draped in a sterile fashion using 3 cycles of surgical
scrub and alcohol/chlorhexidine rinse. The level of anesthesia will
be monitored by heart rate, respiration rate, temperature, animal
movement, pupillary size, toe pinch reflex, blinking reflex, fluid
balance tearing, and salivation. Additional doses of KAX (0.3
ml/kg) will be given to maintain general anesthesia. An incision
will be made in the hindlimb of the rabbit to expose the femoral
artery for catheterization. A slit will be cut in the artery with
micro-scissors and a 4F introducer sheath will be placed into the
femoral artery and secured in place with a 4.0 silk suture. A 3F
angiographic catheter and a guidewire will then be advanced with
fluoroscopic guidance towards the right kidney until
catheterization of the renal artery is achieved (1.5-3.5 mm
diameter). Digital subtraction angiography will be performed to
confirm proper placement of the catheter (FIG. 8).
[0101] After the previously obtained autologous thrombus has
matured for 1 hour, it will be cut into 2 sections and a section
will be placed into a 0.9% saline filled syringe for embolization.
The thrombus segment and saline will then be injected into the
lower branch of the right renal artery. Without moving the
catheter, the second clot segment will be injected. Successful
thromboembolism of the renal artery will be confirmed with
angiography (FIG. 9). The left renal artery will then be
catheterized with the same technique. The same procedure as
described above will be repeated in the left renal artery. All of
the animals will remain under general anesthesia for 30 minutes
after thrombus injection, but before initiating any treatment.
[0102] Final angiography will be performed bilaterally 4 hours
after clot injection to determine recanalization status and will be
graded with the TIMI (Thrombosis in Myocardial Infarction) score,
which is a commonly used system for grading recanalization. The
animal will be euthanized with an overdose of sodium pentobarbital.
The kidneys will be surgically removed, sliced into 5 mm sections
and allowed to soak in TTC stain for 30 minutes. The specimens will
then be digitally photographed (FIG. 10) and the infarction percent
of each kidney will be calculated.
[0103] It should be understood that the examples and embodiments
described herein are for illustrative purposes only and that
various modifications or changes in light thereof will be suggested
to persons skilled in the art and are to be included within the
spirit and purview of this application.
* * * * *