U.S. patent application number 16/439899 was filed with the patent office on 2019-10-31 for embolization microcatheter.
The applicant listed for this patent is ACCURATE MEDICAL THERAPEUTICS LTD.. Invention is credited to Eran MILLER, Michael Gabriel TAL.
Application Number | 20190329000 16/439899 |
Document ID | / |
Family ID | 55272528 |
Filed Date | 2019-10-31 |
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United States Patent
Application |
20190329000 |
Kind Code |
A1 |
TAL; Michael Gabriel ; et
al. |
October 31, 2019 |
EMBOLIZATION MICROCATHETER
Abstract
Microcatheter for delivering a substance (e.g., infusion agent
including embolization material and/or contrast enhancing material)
in a small blood vessel towards a target bodily part. Includes a
single lumen surrounded by tubular wall having outer diameter and
opened at both ends; tubular wall proximal portion is connectable
to a pressure source and reservoir containing infusion agent, and
tubular wall distal portion ends with a tip; the tubular wall
distal portion includes an infusion agent flow disruption section
configured to disrupt passage therethrough of incoming retrograded
flow of infusion agent, during continuous delivery of infusion
suspension from the reservoir to the tip. Disclosed are methods
using the microcatheter for performing local embolization in a
small blood vessel feeding a (for example, cancerous) target bodily
part, and for delivering infusion agent in a small blood vessel
towards such target bodily part. Also disclosed are devices and
methods for filtering non-target infusion agent.
Inventors: |
TAL; Michael Gabriel;
(Savyon, IL) ; MILLER; Eran; (Moshav Beit Elazari,
IL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
ACCURATE MEDICAL THERAPEUTICS LTD. |
Tel-Aviv |
|
IL |
|
|
Family ID: |
55272528 |
Appl. No.: |
16/439899 |
Filed: |
June 13, 2019 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
15542427 |
Jul 9, 2017 |
10398875 |
|
|
PCT/IB2016/050087 |
Jan 8, 2016 |
|
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16439899 |
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62101637 |
Jan 9, 2015 |
|
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62127036 |
Mar 2, 2015 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 2017/00893
20130101; A61B 17/12109 20130101; A61M 25/0068 20130101; A61M
25/0074 20130101; A61M 2025/0096 20130101; A61B 2017/00345
20130101; A61B 2017/00884 20130101; A61M 2205/7545 20130101; A61M
25/0021 20130101; A61M 2025/0073 20130101; A61B 17/12186 20130101;
A61M 25/0054 20130101; A61M 25/0075 20130101; A61M 5/007 20130101;
A61M 2025/0024 20130101; A61B 2017/1205 20130101; A61M 2025/0042
20130101; A61M 2025/0057 20130101; A61M 2025/0079 20130101; A61M
25/007 20130101; A61M 31/005 20130101; A61M 25/0067 20130101 |
International
Class: |
A61M 25/00 20060101
A61M025/00; A61M 5/00 20060101 A61M005/00; A61B 17/12 20060101
A61B017/12 |
Claims
1) A kit comprising: an embolization microcatheter comprising: (a)
a tip having a distal outlet configured for allowing outflow of
embolization; and (b) a filter section comprising a plurality of
openings formed around and along a wall of said filter section; and
embolization particles; wherein the filter section is configured
for allowing selective lateral outflow of fluid while preventing
outflow of the embolization particles.
2) The kit of claim 1, wherein the filter section is more flexible
than that of other wall portions of the embolization
microcatheter's wall.
3) The kit of claim 1, wherein the microcatheter has an outer
diameter equal to or less than about 1 mm.
4) The kit of claim 1, wherein the embolization particles have a
diameter ranging from 100 microns to 1500 microns
5) The kit of claim 1, wherein a width of each of said plurality of
openings is equal to or less than about 100 microns
6) The kit of claim 1, further comprising a suspension fluid.
7) The kit of claim 6, wherein the embolization particles are
suspended in the suspension fluid.
8) The kit of claim 1, further comprising a contrast enhancing
agent.
9) The kit of claim 8, wherein the contrast enhancing agent is
suspended in the suspension fluid.
10) The kit of claim 8, wherein the contrast enhancing agent
comprises lipiodol, iodixanol or iohexol.
11) The kit of claim 1, wherein the embolization particles
comprises non-spherical particles, or microspheres.
12) The kit of claim 1, wherein a total opened cross section of the
plurality of openings is equal to or greater than a cross section
of the distal outlet.
13) The kit of claim 1, wherein the microcatheter is configured as
a single integrated structure.
14) The kit of claim 1, wherein the plurality of openings is in the
form of slits or pores.
15) The kit of claim 1, wherein the plurality of openings have a
circular or rectangular cross section.
16) The kit of claim 1, wherein the plurality openings comprises
burst slit configured to open when under a predetermined pressure
or force.
17) The kit of claim 1, wherein the plurality of openings comprises
constantly open slit.
Description
RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 15/542,427 filed on Jul. 9, 2017, which claims
the benefit of National Phase PCT Patent Application No.
PCT/IB2016/050087, filed Jan. 8, 2016, which claims priority to
U.S. Provisional Application No. 62/101,637 filed on Jan. 9, 2015
and U.S. 62/127,036 filed Mar. 2, 2015. The contents of the above
applications are all incorporated by reference as if fully set
forth herein in their entirety.
FIELD OF THE INVENTION
[0002] The present invention, in some embodiments thereof, relates
to microcatheters and methods for delivering a substance (e.g., an
infusion agent including embolization material and/or contrast
enhancing material) to a target bodily part, for example, located
within the cardiovascular system, and in particular to an
embolization microcatheter, uses thereof in performing local
embolization procedures, and delivering an infusion agent (for
example, embolization beads with contrast enhancing material). Some
embodiments of the invention are applicable for: (i) delivering an
infusion agent including embolization material and/or contrast
enhancing material in a small blood vessel towards a target bodily
part, and (ii) performing local embolization in a small blood
vessel feeding a (for example, cancerous) target bodily part,
thereby forming emboli in small blood vessels, while preventing or
minimizing non-target embolization (associated with contrast
enhancing material). Some embodiments of the invention also relate
to devices and methods for filtering non-target infusion agent
(e.g., embolization material and/or contrast enhancing
material).
BACKGROUND OF THE INVENTION
[0003] The purpose of embolization is to prevent blood flow to an
area of the body, which can effectively shrink a tumor or block an
aneurysm, commonly carried out as an endovascular procedure. Access
to the organ in question is acquired by means of a guidewire and
catheter(s). The position of the correct artery or vein supplying
the pathology in question can be located by digital subtraction
angiography (DSA), producing images are then used as an accessing
map to the correct vessel. The artificial embolus can be made by
using coils, particles, foam, plug, microspheres or beads. Once the
artificial emboli have been successfully introduced, another set of
DSA images are taken to confirm a successful deployment.
[0004] Transarterial embolization therapy, tumor embolization, or
transcatheter arterial embolization (TAE), involve administration
of embolization material (which may include chemotherapeutics
or/and radiotherapeutics) directly to a tumor typically associated
with a target bodily part, such as an organ (for example, the
liver), via a catheter. These techniques are usually performed
using a microcatheter which targets the tumor, while attempting to
avoid dispersion of embolization material to healthy organs.
[0005] Embolization of tumors is usually performed using
microcatheters for different reasons. At first, there is a
requirement for localized embolization for effecting primarily the
tumor and as little healthy tissue as possible. One of the problems
associated with embolization is commonly known as "non-target
embolization", where the embolic material travels to small blood
vessels other than to those which directly feed the target tumor or
region. This can damage healthy tissues in these areas, often
resulting in serious complications. Possible scenarios include
gastric ulcers with liver embolization, as well as cases where
embolic material refluxes alongside the microcatheter reaching the
wall of the stomach, possibly causing ischemia and ulceration. An
additional phenomenon, which is abundant, especially, in advanced
stage liver cancer, is non-target embolization through
arterioportal shunt.
[0006] A microcatheter is usually passed via a larger-lumen
catheter, which is placed within the proximal part of the vessel,
such as the celiac or hepatic artery, and the microcatheter is then
advanced therethrough towards the tumor until reaching an effective
distance for the embolization. It is advantageous to use a
diagnostic catheter as the delivery medium for the microcatheter,
by not replacing it with a larger diameter sheath, for example,
therefore saving substantial time. The inner lumen of the
diagnostic catheter is very small, usually 0.035 and up to 0.038
inches, so that the microcatheter should be about 1 mm or less in
outer diameter.
[0007] Another reason that microcatheters are routinely used in
embolization procedures is the size of the feeding vessels, which
carry blood directly to the organ and tumor. In order to get as
close as possible to the tumor, the embolization catheter is
advanced into smaller and sometime tortuous vessels. These vessels
cannot be accessed with a larger and often stiffer catheter. Also,
blood vessels in the body tend to go into spasm when manipulated,
causing an ineffective embolic material delivery, so flexible
micro-sized catheters are preferred to avoid such scenarios.
SUMMARY OF THE INVENTION
[0008] The present invention, in some embodiments thereof, relates
to microcatheters and methods for delivering a substance (e.g., an
infusion agent including embolization material and/or contrast
enhancing material) to a target bodily part, for example, located
within the cardiovascular system, and in particular to an
embolization microcatheter, uses thereof in performing local
embolization procedures, and delivering an infusion agent (for
example, embolization beads with contrast enhancing material). Some
embodiments of the invention are applicable for: (i) delivering an
infusion agent including embolization material and/or contrast
enhancing material in a small blood vessel towards a target bodily
part, and (ii) performing local embolization in a small blood
vessel feeding a (for example, cancerous) target bodily part,
thereby forming emboli in small blood vessels, while preventing or
minimizing non-target embolization (associated with contrast
enhancing material). Some embodiments of the invention also relate
to devices and methods for filtering non-target infusion agent
(e.g., embolization material and/or contrast enhancing
material).
[0009] According to an aspect of some embodiments of the present
invention, there is provided an embolization microcatheter for
delivering an infusion agent in a small blood vessel towards a
target bodily part, the microcatheter comprising: a single lumen
surrounded by a tubular wall having an outer diameter and opened at
both ends; a proximal portion of the tubular wall is connectable to
a pressure source and to a reservoir configured for containing an
infusion suspension of the infusion agent in an infusion fluid, and
a distal portion of the tubular wall ends with a tip; the tubular
wall distal portion comprises an infusion agent flow disruption
section applicable via the lumen and configured, when applied, to
disrupt passage of an incoming retrograded flow of the infusion
agent around periphery of the tubular wall distal portion adjacent
thereto, during a continuous delivery of the infusion suspension
from the reservoir to the tip. The use of a microcatheter having a
single lumen only, for delivering the infusion suspension together
with disrupting retrograded flow, optionally selectively or in
reaction to change is surroundings (e.g., elevation of ambient
pressure above a certain degree), is advantageous, for example, for
keeping the microcatheter structure as small as possible, therefore
having it fit for passage through a larger-sized catheter or/and
into small blood vessels.
[0010] According to some embodiments of the invention, the flow
disruption section is configured to diminish velocity of the
incoming retrograded flow of the infusion agent, to divert or block
the incoming retrograded flow of the infusion agent, to cause
turbulence or vortex in the incoming retrograded flow of the
infusion agent, or/and to increase local pressure thereabout.
[0011] According to some embodiments of the invention, the flow
disruption section is configured for the disruption by injecting a
portion of the infusion fluid against the retrograded flow, the
flow disruption section comprises a plurality of openings
distributed around or/and along the flow disruption section, each
opening is shaped or/and sized to allow passage therethrough of the
infusion fluid of the infusion suspension, and to block passage
therethrough of the infusion agent of the infusion suspension.
[0012] According to some embodiments of the invention, at least one
of the openings comprises a slit with a gap having a maximal cross
sectional dimension less than minimal diameter of the infusion
agent. According to some embodiments of the invention, at least one
of the openings comprises a pore having a maximal cross sectional
dimension less than minimal diameter of the infusion agent.
[0013] According to some embodiments of the invention, the maximal
cross sectional dimension is equal to or less than about 100
microns, or optionally is equal to or less than about 30 microns.
According to some embodiments of the invention, the pore is located
at end of a channel being angled relative to a long axis of the
lumen or/and relative to a radial axis thereof at a cross section
adjacent thereto.
[0014] According to some embodiments of the invention, the
microcatheter includes at least two of the pores angularly located
in different directions such that a first stream of the infusion
fluid in immediate vicinity of a first one of the pores at least
partially intersects a second stream of the infusion fluid in
immediate vicinity of a second one of the pores.
[0015] According to some embodiments of the invention, the flow
disruption section comprises material being firmer than material of
other sections of the tubular wall distal portion. According to
some embodiments of the invention, the flow disruption section is
made of a metallic material, a hard polymeric material, or a
combination thereof.
[0016] According to some embodiments of the invention, the flow
disruption section comprises a plurality of projections branching
out from and distributed around or/and along the flow disruption
section. According to some embodiments of the invention, the
projections are flexible. According to some embodiments of the
invention, the projections are configured to bend proximally into a
straight form along the tubular wall distal portion when the flow
disruption section is passed distally within a closely fitting
outer tube. According to some embodiments of the invention, the
projections are curled distally towards the tip when in a relaxed
configuration. According to some embodiments of the invention, the
projections are in a form of threads, prongs, or bulges.
[0017] According to some embodiments of the invention, the flow
disruption section comprises material being thinner than material
of other sections of the tubular wall distal portion. According to
some embodiments of the invention, the flow disruption section
comprises material being more flexible than material of other
sections of the tubular wall distal portion. According to some
embodiments of the invention, the microcatheter is configured as a
single integrated structure, wherein the tubular wall includes, and
is structurally continuous with, the flow disruption section as a
single member.
[0018] According to some embodiments of the invention, the tubular
wall outer diameter is equal to or less than about 1 mm. According
to some embodiments of the invention, the tubular wall is
configured for insertion into the small blood vessel originating
from a celiac or hepatic artery. According to some embodiments of
the invention, the tubular wall is configured for the delivery of
the infusion agent to the target bodily part being a tumor or
cancerous tissue.
[0019] According to some embodiments of the invention, the flow
disruption section is shaped to induce turbulent flow in distal
approximation thereto upon flow of the infusion agent away from the
target bodily part and towards the tip of the tubular wall distal
portion. According to some embodiments of the invention, the
tubular wall distal portion tip includes the flow disruption
section.
[0020] According to some embodiments of the invention, the flow
disruption section is pressure sensitive and configured to disrupt
the incoming retrograded flow of the infusion agent only when
pressure inside the tubular wall distal portion equals a
predetermined pressure.
[0021] According to some embodiments of the invention, the
microcatheter further comprises a valve mechanism configured to
cover side openings provided at the flow disruption section when
pressure inside the tubular wall distal portion is less than the
predetermined pressure, and to uncover the side openings when
pressure inside the tubular wall distal portion is greater than the
predetermined pressure.
[0022] According to some embodiments of the invention, the flow
disruption section is configured to stretch from a first average
diameter to a second average diameter greater than the tubular wall
outer diameter when pressure inside the tubular wall distal portion
equals the predetermined pressure, and to collapse back to the
first average diameter when the pressure inside the tubular wall
distal portion is less than the predetermined pressure, during the
continuous delivery of the infusion suspension from the reservoir
to the tip before, during, and after the stretching and
collapsing.
[0023] According to some embodiments of the invention, the tubular
wall is sized for unhindered insertion into the small blood vessel
having a first average ambient pressure upon the tubular wall
placement therein, and configured for the delivery of the infusion
suspension thru the lumen and the tip when the pressure inside the
tubular wall distal portion is a first inner pressure being less
than the predetermined expansion pressure and greater than the
first average ambient pressure, wherein the flow disruption section
is configured such that upon elevation to a second average ambient
pressure within the small blood vessel, being equal to or greater
than the first inner pressure, and upon accumulation of the
infusion suspension between the tip and the target bodily part, the
pressure inside the tubular wall distal portion increases to a
second inner pressure being equal to or greater than the
predetermined expansion pressure, whereby the flow disruption
section stretches to the second average diameter.
[0024] According to some embodiments of the invention, the
microcatheter is configured such that, under a selected third inner
pressure being greater than the first inner pressure and less than
the second inner pressure, the flow disruption section stretches in
response to a systole and collapses in response to a diastole,
relative to the second average ambient pressure. According to some
embodiments of the invention, the predetermined pressure is greater
than 50 mm Hg.
[0025] According to some embodiments of the invention, the flow
disruption section is configured to expand from the first average
diameter to a maximal average diameter greater than inner diameter
of the small blood vessel in direct blood communication with the
target bodily part. According to some embodiments of the invention,
the flow disruption section is configured to expand to a maximal
average diameter being less than inner diameter of the small blood
vessel in direct blood communication with the target bodily
part.
[0026] According to some embodiments of the invention, the flow
disruption section comprises material being permeable to the
infusion fluid and impermeable to the infusion agent, such that
when the flow disruption section stretches to the second average
diameter, the impermeable material allows flowing of the infusion
fluid therethrough and prevents passage and flowing of the infusion
agent therethrough.
[0027] According to some embodiments of the invention, the flow
disruption section includes a sub-section having at least one
opening sized to allow passage therethrough of the infusion agent
when the flow disruption section is at least partially stretched.
According to some embodiments of the invention, the at least one
opening is configured to obstruct and prevent flow therethrough of
the infusion agent when the flow disruption section is at the first
average diameter. According to some embodiments of the invention,
the at least one opening is directed at least partially in a distal
direction of the tubular wall or/and towards the tip.
[0028] According to an aspect of some embodiments of the present
invention, there is provided a method for performing local
embolization in a small blood vessel feeding a cancerous target
bodily part, the method comprising: providing an embolization
microcatheter comprising a tubular wall having an outer diameter,
enclosing a single lumen extending therealong, and including a
distal portion ending with a tip opened to the lumen with a distal
outlet, the tubular wall distal portion comprises an infusion agent
flow disruption section applicable via the lumen and configured to
disrupt passage around periphery of the distal portion of an
incoming retrograded flow of infusion agent, during a continuous
delivery of an infusion suspension of the infusion agent in an
infusion fluid through the lumen to the tip; locating the target
bodily part and the small blood vessel using an imaging technique;
providing a catheter in close proximity to a proximal entry to the
small blood vessel or to an interim blood vessel opened to the
small blood vessel downstream thereto, the catheter comprises a
hollow passage opened to the small blood vessel and has an inner
diameter equal to or less than about 1 mm; passing the
microcatheter through the hollow passage and into the small blood
vessel, whereby the small blood vessel reaches a first average
ambient pressure upon the tubular wall placement therein;
delivering the infusion suspension through the lumen and the distal
outlet to the target bodily part; accumulating the infusion
suspension between the microcatheter tip and the target bodily
part, characterized by an increase of pressure within the small
blood vessel to a second average ambient pressure; and allowing
or/and applying the infusion agent flow disruption section to
disrupt an incoming retrograded flow of the infusion agent passing
therethrough during the continuous delivery of the infusion
suspension through the lumen to the tip, by diminishing, blocking
or/and causing turbulence in the incoming retrograded flow of the
infusion agent.
[0029] According to some embodiments of the invention, in the
method, the flow disruption section comprises a plurality of
openings distributed around or/and along the flow disruption
section, each opening is shaped or/and sized to allow passage
therethrough of the infusion fluid of the infusion suspension, and
to block passage therethrough of the infusion agent, in a form of
beads, of the suspension, wherein the delivering comprises infusing
a volume of the infusion fluid through the side openings while
blocking the beads from passing through the side openings, whereby
during the allowing, the infused volume of the infusion fluid
effects the disrupting of the incoming retrograded flow of the
infusion agent.
[0030] According to some embodiments of the invention, in the
method, the infusion agent flow disruption section is pressure
sensitive, wherein the method further includes: pressurizing the
lumen so as to allow the pressure inside the tubular wall distal
portion to become equal to or exceed a predetermined pressure,
whereby the flow disruption section stretches outwardly and effects
the disruption of the passage therethrough of the incoming
retrograded flow of the infusion agent, during the continuous
delivery of the infusion suspension through the lumen to the
tip.
[0031] According to some embodiments of the invention, in the
method, the pressurizing actuates the flow disruption section to
diminish, block, or/and cause turbulence in, the incoming
retrograded flow of the infusion agent, thereby increasing local
pressure thereabout. According to some embodiments of the
invention, in the method, the pressurizing is performed until the
infusion agent occludes the small blood vessel or/and until a
selected pressure difference is developed between the tubular wall
distal portion and the target bodily part.
[0032] According to some embodiments of the invention, the method
comprises repeating at least one of the accumulating and the
pressurizing until forming a chosen sized embolus between the tip
and the target bodily part.
[0033] According to some embodiments of the invention, in the
method, the locating includes delivering contrast enhancing
material to the small blood vessel through the hollow passage of
the catheter.
[0034] According to an aspect of some embodiments of the present
invention, there is provided a method for performing local
embolization in a small blood vessel feeding a cancerous target
bodily part, the method comprising: providing an embolization
microcatheter comprising a tubular wall having an outer diameter,
enclosing a single lumen extending therealong, and comprising a
distal portion ending with a tip opened to the lumen with a distal
outlet, the tubular wall distal portion comprises an infusion agent
flow disruption section applicable via the lumen and configured to
disrupt passage therethrough of an incoming retrograded flow of an
infusion agent, during continuous delivery of an infusion
suspension of the infusion agent in an infusion fluid through the
lumen to the tip; passing the microcatheter into the small blood
vessel until the tip of the microcatheter is located at a chosen
distance from the target bodily part; delivering the infusion
suspension via the distal outlet towards the target bodily part;
allowing or/and applying the infusion agent flow disruption section
to disrupt an incoming retrograded flow of the infusion agent
passing therethrough during the continuous delivery of the infusion
suspension through the lumen to the tip, by diminishing, blocking
or/and causing turbulence in the incoming retrograded flow of the
infusion agent; selecting a blood vessel portion upstream to the
small blood vessel, and monitoring the blood vessel portion using
an imaging technique; via the monitoring, detecting an indication
of presence of the infusion fluid in the blood vessel portion; and
in response to the detected indication, stopping the delivery of
the infusion suspension.
[0035] According to some embodiments of the invention, in the
method, the selecting of the blood vessel portion includes
determining a required distance from the small blood vessel with a
minimal effectively imaged quantity of the infusion fluid volume
originating from the side openings and flowing into the blood
vessel portion, before the infusion suspension originating from the
distal outlet and reaching the blood vessel portion following blood
flow reflux from the small blood vessel towards the blood vessel
portion.
[0036] According to some embodiments of the invention, in the
method, the required distance is at least about 10 mm. According to
some embodiments of the invention, in the method, the infusion
fluid includes a contrast enhancing agent. According to some
embodiments of the invention, in the method, the infusing occurs
following blood flow reflux from the small blood vessel towards the
blood vessel portion. According to some embodiments of the
invention, in the method, the infusing occurs during the delivery
of the infusion suspension.
[0037] Unless otherwise defined, all technical or/and scientific
terms used herein have the same meaning as commonly understood by
one of ordinary skill in the art to which the invention pertains.
Although methods and materials similar or equivalent to those
described herein can be used in the practice or testing of
embodiments of the invention, exemplary methods or/and materials
are described below. In case of conflict, the patent specification,
including definitions, will control. In addition, the materials,
methods, and examples are illustrative only and are not intended to
be necessarily limiting.
BRIEF DESCRIPTION OF THE DRAWINGS
[0038] Some embodiments of the invention are herein described, by
way of example only, with reference to the accompanying drawings.
With specific reference now to the drawings in detail, it is
stressed that the particulars shown are by way of example and for
purposes of illustrative discussion of embodiments of the
invention. In this regard, the description taken with the drawings
makes apparent to those skilled in the art how embodiments of the
invention may be practiced.
[0039] In the drawings:
[0040] FIGS. 1A-1G are schematic side cut views representing
possible scenarios of implementing exemplary embodiments of a
method for performing local embolization in a small blood vessel
feeding a target bodily part, in accordance with some embodiments
of the invention;
[0041] FIGS. 2A-2B are schematic side cut views of exemplary
embodiments of a microcatheter during delivery of infusion agent
(e.g., embolization material and/or contrast enhancing material)
before (FIG. 2A) and after (FIG. 2B) occurrence of a retrograded
flow, in accordance with some embodiments of the invention;
[0042] FIG. 3 is a schematic top view of an exemplary embodiment of
an infusion agent flow disruption section having openings in form
of slits, in accordance with some embodiments of the invention;
[0043] FIGS. 4A-4B are schematic side cut views of exemplary
embodiment of a microcatheter including a plurality of projections,
during delivery of infusion agent (e.g., embolization material
and/or contrast enhancing material) before (FIG. 4A) and after
(FIG. 4B) occurrence of a retrograded flow, in accordance with some
embodiments of the invention;
[0044] FIGS. 5A-5D are schematic partial side cut views of
exemplary embodiments of different exemplary projections of an
infusion agent flow disruption section, in accordance with some
embodiments of the invention;
[0045] FIGS. 6A-6D are schematic side cut views of exemplary
embodiments of a microcatheter in different scenarios, particularly
highlighting an exemplary infusion agent flow disruption section
included in the microcatheter tubular wall distal portion, in
accordance with some embodiments of the invention;
[0046] FIGS. 7A-7C are schematic side cut views of exemplary
embodiments of a microcatheter in different scenarios, particularly
highlighting an exemplary infusion agent flow disruption section
included in the microcatheter tubular wall distal portion, in
accordance with some embodiments of the invention;
[0047] FIGS. 8A-8B are schematic partial side cut views of
exemplary embodiments of a portion of an infusion agent flow
disruption section that includes a covering mechanism, before (FIG.
8A) and after (FIG. 8B) actuation thereof, in accordance with some
embodiments of the invention;
[0048] FIGS. 9A-9B are schematic side cut views of exemplary
embodiments of the distal end of an exemplary microcatheter,
particularly highlighting an exemplary embodiment of a valve
mechanism configured to cover (FIG. 9A) and uncover (FIG. 9B) side
openings included in an infusion agent flow disruption section, in
accordance with some embodiments of the invention; and
[0049] FIGS. 10A-10B are schematic side cut views representing
possible scenarios of implementing exemplary embodiments of a
method for performing local embolization in a small blood vessel
feeding a target bodily part, particularly highlighting detecting
an indication of presence of infusion fluid in a blood vessel
portion upstream to the small blood vessel, in accordance with some
embodiments of the invention.
DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION
[0050] The present invention, in some embodiments thereof, relates
to microcatheters and methods for delivering a substance (e.g., an
infusion agent including embolization material and/or contrast
enhancing material) to a target bodily part, for example, located
within the cardiovascular system, and in particular to an
embolization microcatheter, uses thereof in performing local
embolization procedures, and delivering an infusion agent (for
example, embolization beads with contrast enhancing material). Some
embodiments of the invention are applicable for: (i) delivering an
infusion agent including embolization material and/or contrast
enhancing material in a small blood vessel towards a target bodily
part, and (ii) performing local embolization in a small blood
vessel feeding a (for example, cancerous) target bodily part,
thereby forming emboli in small blood vessels, while preventing or
minimizing non-target embolization (associated with contrast
enhancing material). Some embodiments of the invention also relate
to devices and methods for filtering non-target infusion agent
(e.g., embolization material and/or contrast enhancing
material).
[0051] It is understood that the invention is not limited to the
particular methodology, protocols, and reagents, etc., described
herein, as these may vary as the skilled artisan will recognize. It
is also to be understood that the terminology used herein is used
for the purpose of describing particular embodiments only, and is
not intended to limit the scope of the invention. The following
exemplary embodiments may be described in the context of exemplary
embolization procedures for ease of description and understanding.
However, the invention is not limited to the specifically described
devices and methods, and may be adapted to various clinical
applications without departing from the overall scope of the
invention.
[0052] A limitation of using current micro-sized catheters for
delivering an infusion agent (e.g., including embolization
material, typically, with contrast enhancing material) is their
inability to "push" the embolization material deeper into the tumor
without applying excessive pressures. Over injection or forceful
injection often cause back flow or/and dispersion of the infusion
agent, potentially causing non-target embolization (associated with
contrast enhancing material). Such backward flow or/and dispersion
of embolization material during forceful injection can also be
affiliated with inadvertent repositioning of the catheter.
[0053] In view of the preceding, and other, limitations associated
with current embolization techniques, there is need for developing
and practicing improved or/and new techniques (devices and methods)
for delivering an infusion agent (e.g., including embolization
material and/or contrast enhancing material) into small blood
vessels located in close proximity to a target body part, while
preventing or diminishing infusion agent (embolization material
or/and contrast enhancing material) back flow or reflux from the
small blood vessels.
[0054] The term "infusion agent", as used herein, refers to a
substance that is suspended in a suspension fluid for forming an
infusion suspension. The infusion suspension is supplied to, or
provided in, a reservoir of a catheter and is infused (such as by
injection) into a blood vessel of a subject.
[0055] In exemplary embodiments, the infusion agent is composed of,
or includes, embolization (embolic) material or/and contrast media
(such as contrast enhancing material or agent). In exemplary
embodiments, the infusion agent is composed of, or includes,
embolization (embolic) material, wherein the embolization material,
in addition to having embolization properties, also has
radio-opacity or/and radiographic properties. In exemplary
embodiments, the infusion agent is composed of, or includes,
contrast enhancing material, wherein the contrast enhancing
material, in addition to having radio-opacity or/and radiographic
properties, also has embolization properties. In exemplary
embodiments, the infusion agent may be composed of, or include, any
type or kind, and amount, of other material, having any type or
kind of properties, suitable for infusing into a blood vessel of a
subject.
[0056] In exemplary embodiments, the infusion suspension (including
the infusion agent suspended in the infusion fluid) may be composed
and formulated for being suitable in embolic type therapies, for
example, intra-arterial embolic therapies. In some such
embodiments, the infusion suspension may include the suspended
infusion agent in the form of embolic beads for bland embolization.
Optionally, alternatively or additionally, the infusion suspension
may include the suspended infusion agent in the form of lipidol
mixed with chemotherapeutic agents and embolic beads or/and
chemotherapy drug eluting beads (e.g., polyvinyl alcohol
microspheres loaded with doxorubicin, superabsorbent polymer
microspheres-loaded with doxorubicin, or gelatin
microspheres--loaded with cisplatin) for chemo-embolization.
Optionally, alternatively or additionally, the infusion suspension
may include the suspended infusion agent in the form of radioactive
beads for radio-embolization.
[0057] In exemplary embodiments, embolization material may include
at least one of liquid embolic agents (e.g., Onyx.TM. by Covidien,
n-butyle-2-cyanoacrylate, or ethiodized oil), sclerosing agents
(e.g., ethanol, ethanolamine oleate, or sodium tetradecyl sulfate),
or particulate embolic agents (e.g., hemostatic absorbable gelatin,
polyvinyl alcohol (PVA), acrylic gelatin microspheres, or glass).
Embolization material may include radiopaque beads or/and drug
eluting beads.
[0058] In exemplary embodiments, the suspension fluid includes a
contrast enhancing material (agent), for example, diluted to a
certain degree such as with saline. In some instances, the medical
practitioner may mix together a viscous contrast enhancing material
(agent) with embolization materials comprising saline and
embolization beads (particles) or/and chemotherapeutic beads
(particles), for example in a volumetric ratio of 50:50, thereby
producing a fluidic suspension of beads and contrast enhancing
material (agent) diluted to a chosen degree. In an exemplary
embodiment, the suspension includes drug-eluting beads (DEB),
chemotherapeutic material (e.g., doxorubicin) and contrast
enhancing material. In exemplary embodiments, the contrast
enhancing material (agent) may be, or include, any of various
different types or kinds of contrast media, for example,
Visipaque.TM. (iodixanol), or Omnipaque.TM. (iohexol), among many
other suitable types and kinds of contrast media.
[0059] In a non-limiting manner, numerous other possible
compositions and formulations of the infusion suspension, of the
infusion agent, and of the infusion fluid, are applicable for
implementing embodiments of the invention.
[0060] An aspect of some embodiments of the present invention
relates to an embolization microcatheter for delivering an infusion
agent in a small blood vessel towards a target bodily part. The
microcatheter includes a single lumen surrounded by a tubular wall
having an outer diameter and opened at both ends. The use of a
microcatheter having a single lumen only, for delivering the
infusion suspension together with disrupting retrograded flow,
optionally selectively or in reaction to change is surroundings
(e.g., elevation of ambient pressure above a certain degree), is
advantageous, for example, for keeping the microcatheter structure
as small as possible, therefore having it fit for passage through a
larger-sized catheter or/and into small blood vessels.
[0061] A proximal portion of the tubular wall is connectable to a
pressure source and to a reservoir configured for containing an
infusion suspension of the infusion agent (e.g., including
embolization material and/or contrast enhancing material, and
possibly other material) in an infusion fluid, and distal portion
of the tubular wall ends with a tip. The tubular wall distal
portion includes an infusion agent flow disruption section
applicable via the lumen and configured, when applied, to stretch
from a first average diameter to a second average diameter greater
than the tubular wall outer diameter when pressure inside the
tubular wall distal portion equals a predetermined expansion
pressure and to collapse back to the first average diameter when
the pressure inside the tubular wall distal portion is less than
the predetermined expansion pressure. In some embodiments, the
infusion agent flow disruption section allows continuous delivery
of the infusion suspension from the reservoir to the tip before,
during, and after stretching or/and collapsing thereof. In some
embodiments, the infusion agent flow disruption section of the
microcatheter expands and collapses relative to the tubular wall
outer diameter in accordance with changes of ambient pressures
or/and in relation with inner pressures within the microcatheter
lumen. In some embodiments, the microcatheter is particularly
configured for performing local embolization in a small blood
vessel, such as, for example, for feeding a cancerous target bodily
part.
[0062] Referring now to the drawings, FIGS. 1A-1F schematically
illustrate different side cut views representing possible scenarios
of implementing exemplary embodiments of a method for performing
local embolization in a small blood vessel SBV feeding a target
bodily part TBP, for example, being cancerous. Target bodily part
TBP may be a complete organ, or as shown, part of an organ such as
organ ORG. As shown in FIG. 1A, a possible first or preliminary
step may include the locating of target bodily part TBP and the
small blood vessel SBV using an imaging technique (e.g.,
radiography, such as fluoroscopy). For example, as shown, a
diagnostic catheter 10 can be introduced in a large blood vessel
LBV opening to an interim blood vessel IBV interconnecting with
small blood vessel SBV, having a distal opening 11 thereof oriented
generally towards the proximal entry of interim blood vessel
IBV.
[0063] Contrast enhancing material (agent) CM may be delivered
through diagnostic catheter 10 and opening 11 into interim blood
vessel IBV and small blood vessel SBV in order to facilitate
effective imaging of this anatomy, allowing determination of
different treatment parameters, such as a chosen route or/and
positioning of an embolization microcatheter for accurately and
locally occluding selectively chosen small blood vessels, or even
microcirculation vessels within an entire vascular bed VB, directly
feeding target bodily part TBP. In exemplary embodiments, contrast
enhancing material (agent) CM may be, or include, any of various
different types or kinds of contrast media, for example,
Visipaque.TM. (iodixanol), or Omnipaque.TM. (iohexol), among many
other suitable types and kinds of contrast media.
[0064] Diagnostic catheter 10, or any other catheter, may also be
used for delivering the embolization microcatheter, once it is
provided in approximation with the proximal entry to small blood
vessel SBV. A hollow passage (not shown) opened to interim blood
vessel IBV at opening 11 may have an inner diameter equal to or
less than about 1 mm, as common in diagnostic catheters used in
similar procedures. As shown in FIG. 1B, a microcatheter 12 is
passed (through the hollow passage) into interim blood vessel IBV
and small blood vessel SBV, resulting in a first average ambient
pressure P.sub.am1 in small blood vessel SBV between the distal tip
of microcatheter 12 and target bodily part TBP (i.e.,
P(TBP)=P.sub.am1). In exemplary embodiments, the tip including a
distal outlet 13 of microcatheter 12 is positioned at a chosen
distance X from target bodily part TBP.
[0065] Microcatheter 12, in exemplary embodiments, includes a
single lumen surrounded by a tubular wall 14 having an outer
diameter and opened at both ends. A proximal portion 15 of tubular
wall 14 is connectable (for example, in FIGS. 1B and 1C, shown as
being connected) to a pressure source 16 and to a reservoir 17
configured for containing an infusion suspension made up of an
infusion agent (e.g., embolization material and/or contrast
enhancing material) 18, for example, in a form of beads. A distal
portion 19 of tubular wall 14, which ends with the tip and distal
outlet 13, includes an infusion agent flow disruption section 20
configured to disrupt passage of retrograded flow of the infusion
agent 18 suspended in an infusion fluid (for example, being or
including a contrast enhancing agent), or/and suspended in blood,
flowing outside tubular wall 14 in a distal direction (i.e., in
general direction from distal portion 19 towards proximal portion
15). In some embodiments, infusion agent flow disruption section 20
includes a plurality of side openings distributed around or/and
along it, each opening may be shaped or/and sized to allow passage
therethrough of an infusion fluid, and to block passage
therethrough of the infusion agent (e.g., in a form of beads). Such
openings may be in a form of pores or/and slits, or in any other
relevant form or shape known in the art. In some such embodiments,
delivering of infusion agent 18 through distal outlet 13 includes
infusing a volume of infusion fluid through the side openings while
blocking infusion agent (e.g., beads) from passing
therethrough.
[0066] In exemplary embodiments, additionally or alternatively,
infusion agent flow disruption section 20 is pressure sensitive and
is configured to stretch or/and expand (particularly illustrated,
for example, via FIG. 1E) from a first average diameter to a second
average diameter greater than the tubular wall 14 outer diameter
when pressure inside tubular wall distal portion 19 equals or
exceeds a predetermined expansion pressure PP. In exemplary
embodiments, additionally, infusion agent flow disruption section
20 is configured to collapse back to the first average diameter
when the pressure inside tubular wall 14 distal portion 19 is less
than the predetermined expansion pressure PP. In some embodiments,
infusion agent flow disruption section 20 allows continuous
delivery of infusion agent 18 from reservoir 17 to distal outlet
13--before, during, and after stretching or/and collapsing
thereof.
[0067] In some embodiments, predetermined expansion pressure PP is
greater than about 50 mm Hg, or greater than about 80 mm Hg, or
greater than about 100 mm Hg, or greater than about 120 mm Hg, or
higher, or lower, or an intermediate value.
[0068] Infusion agent 18 may include at least one of liquid embolic
agents (e.g., Onyx.TM. by Covidien, n-butyle-2-cyanoacrylate, or
ethiodized oil), sclerosing agents (e.g., ethanol, ethanolamine
oleate, or sodium tetradecyl sulfate), or particulate embolic
agents (e.g., hemostatic absorbable gelatin, polyvinyl alcohol
(PVA), acrylic gelatin microspheres, or glass). Infusion agent 18
may include radiopaque beads or/and drug eluting beads. In
exemplary embodiments, infusion agent 18 is of particulate form
(e.g., non-spherical particles, or microspheres) having an average
size (long dimension or diameter) in a range of between about 25
microns (.mu.m) and about 1,500 microns (.mu.m). In exemplary
embodiments, infusion agent 18 has a compressibility in a range of
between about 10% and about 40%. For example, polyvinyl alcohol
(PVA) type infusion agent has a compressibility in a range of
between about 20% and about 30%.
[0069] As shown in FIG. 1C, infusion agent 18 is then delivered
through distal outlet 13 to target bodily part TBP. Pressure source
16 can be applied so as to generate a first inner pressure P.sub.i1
inside tubular wall 14 distal portion 19 (i.e., P(19)=P.sub.i1)
being less than predetermined expansion pressure PP and greater
than first average ambient pressure P.sub.am1, thereby delivering
an infusion suspension of infusion agent (e.g., including
embolization material and/or contrast enhancing material) 18
suspended in, and carried by, an infusion (infusion agent carrier)
fluid from reservoir 17 towards target bodily part TBP. Delivered
infusion agent 18 may continue to accumulate between microcatheter
tip and target bodily part TBP, as shown in FIG. 1D, for example as
long as P(19)>P(TBP), at least until increasing pressure P(TBP)
to a second greater average ambient pressure P.sub.am2 being closer
to first inner pressure P.sub.i1. Upon elevation of the pressure
P(TBP) some retrograded flow of infusion agent or/and infusion
fluid or/and blood may occur. A retrograded flow of embolization
material is then halted, diminished, blocked or/and interrupted by
causing turbulence or vortex therein with flow disruption section
20. In some embodiments where flow disruption section 20 includes
side openings, the infused volume of infusion fluid delivered in
parallel or instead of infusion agent delivery through distal
outlet 13 shall increases a local pressure and disrupt incoming
retrograded flow of infusion agent 18.
[0070] FIG. 1E shows a particular scenario in case flow disruption
section 20 is activated (expanded) for disrupting retrograded flow
of infusion agent (e.g., including embolization material and/or
contrast enhancing material). As shown, pressurizing microcatheter
lumen so as to allow distal portion pressure P(19) to become equal
to or to exceed the predetermined expansion pressure PP, forces
pressure sensitive section 20 to stretch until occluding small
blood vessel SBV (where it may reach a maximal average diameter)
or/and until reaching a selected pressure difference P.sub.s
developed between tubular wall distal portion 19 and target bodily
part TBP (i.e., P(TBP)-P(19)=P.sub.s). In some embodiments, the
maximal average diameter is equal to or larger than about 1 mm, or,
equal to or higher than about 2 mm, or, equal to or higher than
about 4 mm, or, equal to or higher than about 6 mm, or higher, or
lower, or an intermediate value.
[0071] While infusion agent flow disruption section 20 may be in
different sizes or forms, delivery of infusion agent 18 may
continue. The selected pressure difference P.sub.s may be negative,
as shown in FIG. 1F, so further delivery and accumulation of
infusion agent 18 may take place as needed, while infusion agent
flow disruption section 20 remains substantially collapsed. Any of
the preceding steps, for example, the accumulating and
pressurizing, may be repeated until forming a chosen sized embolus
EMB between tip 13 and target bodily part TBP, as shown in FIG.
1G.
[0072] FIGS. 2A-2B schematically illustrate side cut views of
exemplary embodiments of an exemplary microcatheter 30 during
delivery of infusion agent 31 before (FIG. 2A) and after (FIG. 2B)
occurrence of a retrograded flow. Microcatheter 30 is sized and
configured for delivering infusion agent 31 in a small blood vessel
towards a target bodily part 32. Microcatheter 30 includes a single
lumen 33 surrounded by a tubular wall 34 having an outer diameter
and opened at both ends. In some embodiments, tubular wall 34 is
sized for unhindered insertion into a small blood vessel, such as a
celiac or hepatic artery. In some embodiments, outer diameter of
microcatheter 30 is equal to or less than about 2 mm, or equal to
or less than about 1 mm. In some embodiments, microcatheter 30 has
an external diameter equal to the diameter of a commercially
available microcatheter, such as a 2.1 French catheter, or a 2.7
French catheter, or a 2.9 French catheter.
[0073] A proximal portion of tubular wall 34 is connectable to a
pressure source and to a reservoir configured for containing an
infusion suspension of an infusion agent (e.g., embolization
material and/or contrast enhancing material) 31. Infusion agent 31
may include at least one of liquid embolic agents (e.g., Onyx.TM.
by Covidien, n-butyle-2-cyanoacrylate, or ethiodized oil),
sclerosing agents (e.g., ethanol, ethanolamine oleate, or sodium
tetradecyl sulfate), or particulate embolic agents (e.g.,
hemostatic absorbable gelatin, polyvinyl alcohol (PVA), acrylic
gelatin microspheres, or glass). In exemplary embodiments, infusion
agent 31 is of particulate form (e.g., non-spherical particles, or
microspheres) having an average size (long dimension or diameter)
in a range of between about 25 microns (.mu.m) and about 1,500
microns (.mu.m). In exemplary embodiments, infusion agent 31 has a
compressibility in a range of between about 10% and about 40%. For
example, polyvinyl alcohol (PVA) type infusion agent has a
compressibility in a range of between about 20% and about 30%.
[0074] A distal portion of tubular wall ends with a tip 35,
enclosing a distal outlet 36. Tubular wall 34 distal portion
includes an infusion agent flow disruption section 37 configured to
disrupt passage of an incoming retrograded (in a general distal
direction) flow 38 of the infusion agent around tubular wall 34,
during continuous delivery of the infusion agent 31 from the
reservoir to tip 35 and out through distal outlet 36. As shown in
FIG. 2B, flow disruption section 37 is configured to diminish, or
block, incoming retrograded flow 38 of the infusion agent 31, for
example, thereby increasing local pressure thereabout or/and
creating local turbulence or vortex. In some embodiments, the
turbulence or vortex is created by infusion fluid injected or
otherwise expelled from the microcatheter, for example, wherein the
infusion agent 31 is partially or fully filtered from the infusion
fluid.
[0075] Flow disruption section 37 includes a plurality of openings
39 distributed around or/and along it, each opening is shaped
or/and sized to effect passage therethrough of an infusion fluid
(such as a viscous fluid) 40, and to block passage therethrough of
the infusion agent 31. In exemplary embodiments, infusion fluid 40
includes a contrast enhancing material (agent), for example,
diluted to a certain degree such as with saline. In some instances,
the medical practitioner may mix together a viscous contrast
enhancing material (such as a contrast enhancing material or agent)
with embolization material (for example, including saline and
embolization beads), for example, in a volumetric ratio of 50:50,
thereby producing an infusion suspension of embolization beads and
contrast enhancing material or agent diluted to a chosen degree. In
an exemplary embodiment, the infusion suspension includes
drug-eluting beads (DEB), chemotherapeutic material (e.g.,
doxorubicin) and contrast enhancing material. In exemplary
embodiments, the contrast enhancing material (agent) (such as
contrast enhancing material (agent) CM shown in FIG. 1A) may be, or
include, any of various different types or kinds of contrast media,
for example, Visipaque.TM. (iodixanol), or Omnipaque.TM. (iohexol),
among many other suitable types and kinds of contrast media.
[0076] One or more opening 39 includes a pore having a cross
sectional dimension less than minimal diameter of the infusion
agent, for example, embolization material (e.g., bead diameter).
Such cross sectional dimension is, for example, less than about 500
microns (.mu.m), or, equal to or less than about 100 microns
(.mu.m), or, equal to or less than about 40 microns (.mu.m). In
exemplary embodiments, the cross section dimension is in a range of
between about 20 microns (.mu.m) and about 30 microns (.mu.m), for
example, about 28 microns (.mu.m). For example, as shown, each pore
is located at end of a channel being angled (wherein the angle is
an exemplary range of between about 0 degrees and about 90 degrees)
relative to a long axis of lumen 33 or/and relative to a radial
axis thereof at a cross section adjacent thereto. In exemplary
embodiments, at least two pores are angularly located in different
directions such that a first stream of the infusion suspension in
immediate vicinity of a first pore at least partially intersects a
second stream of the infusion suspension in immediate vicinity of a
second pore. Openings 39 or pores may be in any possible form, for
example, with circular or rectangular cross section, or as a burst
slit (i.e., opened only under chosen pressure or force), or a
constantly opened slit. In such exemplary embodiments, the openings
39 or pores have a minimal cross sectional dimension being less
than the minimal diameter of the infusion agent (e.g., embolization
material, (for example, in the form of beads).
[0077] In some embodiments, lumen 33 is configured to deliver a
suspension of infusion fluid 40 and infusion agent 31, for example,
in a form of beads. In some embodiments, distal outlet 36 is shaped
or/and sized to effect passage therethrough of the infusion
suspension of infusion fluid 40 and the infusion agent (beads) 31,
and at least one side opening 39 is shaped or/and sized to effect
passage therethrough of infusion fluid 40, and to block passage
therethrough of infusion agent (beads) 31, for example, if a cross
sectional dimension of the pore in each opening is less than a
minimal diameter of the infusion agent (beads).
[0078] In some embodiments, at least one side opening 39 is shaped
or/and sized to effect passage therethrough of infusion fluid 40,
and to block passage therethrough of infusion agent (beads) 31,
during flow of the infusion suspension through distal outlet 36. In
some other embodiments, at least one side opening 39 is shaped
or/and sized to effect passage therethrough of infusion fluid 40,
and to block passage therethrough of infusion agent (beads) 31,
during conditions when the infusion suspension is blocked or
interrupted from flowing through distal outlet 36.
[0079] In some embodiments, a total opened cross section of all
openings 39 is equal to or greater than a smallest cross section of
lumen 33 and distal outlet 36.
[0080] In some embodiments, infusion fluid 40 at normal body
temperature has an average viscosity of at least about 0.8 mPas, or
at least about 5 mPas, or at least about 10 mPas, or at least about
20 mPas. In exemplary embodiments, infusion fluid 40 is pre-heated,
for example, to a temperature higher than about 37.degree. C.,
before reaching tubular wall 34 distal portion in lumen 33. In
exemplary embodiments, infusion fluid 40 includes, or is mixed
with, another infusable fluid (e.g., glucose water), for example,
also pre-heated with infusion fluid 40 or separately
pre-heated.
[0081] In some embodiments, a farthest distal side opening 39 is
located within a range of between about 0 mm and about 20 mm, or
within a range of between about 0 mm and about 10 mm, or within a
range of between about 0 mm and about 5 mm, proximally to distal
outlet 36.
[0082] FIG. 3 schematically illustrates a top view of an exemplary
embodiment of an infusion agent flow disruption section 55
(included in an exemplary microcatheter 50) having openings in form
of slits. Microcatheter 50 is sized and configured for delivering
infusion agent, for example, including embolization material (e.g.,
in a form of beads) in a small blood vessel, towards a target
bodily part. Microcatheter 50 includes a tubular wall 52 having a
distal portion which ends with a tip 53, enclosing a distal outlet
54. Tubular wall 52 distal portion includes an infusion agent flow
disruption section 55 configured to disrupt passage therethrough of
an incoming retrograded flow of the infusion agent, for example,
during continuous delivery of the infusion agent through distal
outlet 54. Flow disruption section 55 is configured to block,
or/and cause turbulence in, incoming retrograded flow of the
infusion agent, thereby increasing local pressure thereabout.
[0083] Flow disruption section 55 includes a plurality of openings
56 distributed around or/and along it, each opening includes a slit
with a gap having a cross sectional dimension (e.g., width) less
than minimal diameter of the infusion agent. In exemplary
embodiments, another cross sectional dimension of this gap (e.g.,
length) is substantially greater than the minimal diameter of the
infusion agent. In some embodiments, each opening is shaped or/and
sized to effect passage therethrough of an infusion fluid, and to
block passage therethrough of the infusion agent.
[0084] In some embodiments, flow disruption section 55 includes
material being firmer than material of other sections of tubular
wall 52 distal portion. In exemplary embodiments, flow disruption
section 55 is made of a metallic material, a hard polymeric
material, or a combination thereof. In exemplary embodiments, flow
disruption section 55 is coated with a radiopaque material such as
with hydrophilic coating. In exemplary embodiments, flow disruption
section 55 is structured with a metal coil, for example,
impregnated with solid structure or/and attached to a layer of
solid structure.
[0085] FIGS. 4A-4B schematically illustrate side cut views of
exemplary embodiments of a microcatheter 60 including a plurality
of projections, during delivery of infusion agent (e.g.,
embolization material) before (FIG. 4A) and after (FIG. 4B)
occurrence of a retrograded flow. Microcatheter 60 is sized and
configured for delivering the infusion agent, for example,
embolization material (e.g., in a form of beads) in a small blood
vessel, towards a target bodily part. Microcatheter 60 includes a
tubular wall 61 having a distal portion which ends with a tip 62,
enclosing a distal outlet 63. In some embodiments, tubular wall 61
is sized for unhindered insertion into a small blood vessel, such
as a celiac or hepatic artery. In some embodiments, outer diameter
of microcatheter 60 is equal to or less than about 2 mm, or equal
to or less than about 1 mm. In some embodiments, microcatheter 60
has an external diameter equal to the diameter of a commercially
available microcatheter, such as a 2.1 French catheter, a 2.7
French catheter, or a 2.9 French catheter.
[0086] Tubular wall 61 distal portion includes an infusion agent
flow disruption section 64 configured to disrupt passage of an
incoming retrograded flow of the infusion agent, during continuous
delivery of the infusion agent through distal outlet 63. Flow
disruption section 64 is configured to diminish, block, or/and
cause turbulence or vortex in, incoming retrograded flow of the
infusion agent in a distal direction around Tubular wall 61 distal
portion adjacent thereto, and optionally increase local pressure
thereabout.
[0087] Flow disruption section 64 includes a plurality of
projections 65 branching out from and distributed around or/and
along it. In exemplary embodiments, projections 65 are flexible
or/and configured to bend proximally into a straight form along
tubular wall 61 distal portion when flow disruption section 64 is
passed distally within a closely fitting outer tube. In exemplary
embodiments, projections 65 are curled distally towards tip 62 when
in a relaxed configuration such as in absence of retrograded
flow.
[0088] FIGS. 5A-5D schematically illustrate partial side cut views
of exemplary embodiments of different exemplary projections of an
infusion agent flow disruption section. FIG. 5A shows projections
66 in a form of threads angled distally at least when in relaxed
configuration, FIG. 5B shows projections 67 in a form of threads
angled proximally at least when in relaxed configuration, FIG. 5C
shows projections 68 in a form of prongs, and FIG. 5D shows
projections 69 in a form of bulges, for example, as a result of a
coil wounded over the low disruption section.
[0089] Reference is now made to FIGS. 6A-6D, which schematically
illustrate side cut views of exemplary embodiments of a
microcatheter 70 in different scenarios, particularly highlighting
an exemplary infusion agent flow disruption section included in the
microcatheter tubular wall distal portion. Microcatheter 70
includes a single lumen 71 surrounded by a tubular wall 72 having
an outer diameter 73 and opened at both ends. In some embodiments,
tubular wall 72 is sized for unhindered insertion into a small
blood vessel 73, such as a celiac or hepatic artery. In some
embodiments, outer diameter 73 is equal to or less than about 2 mm,
or, equal to or less than about 1 mm. In some embodiments,
microcatheter 70 has an external diameter equal to the diameter of
a commercially available microcatheter, such as a 2.1 French
catheter, a 2.7 French catheter, or a 2.9 French catheter.
[0090] In some embodiments, tubular wall 72 is configured for
delivering a suspension of infusion agent (e.g., embolization
material and/or contrast enhancing material) in an infusion fluid
to a target bodily part such as a tumor or cancerous tissue. A
proximal portion 74 of tubular wall 72 is connectable to a pressure
source 75 and to a reservoir 76 configured for containing the
suspension of the infusion agent (e.g., embolization material) 77.
Infusion agent 77 may include at least one of liquid embolic agents
(e.g., Onyx.TM. by Covidien, n-butyle-2-cyanoacrylate, or
ethiodized oil), sclerosing agents (e.g., ethanol, ethanolamine
oleate, or sodium tetradecyl sulfate), or particulate embolic
agents (e.g., hemostatic absorbable gelatin, polyvinyl alcohol, or
acrylic gelatin microspheres).
[0091] Distal portion 78 includes an infusion agent flow disruption
section 80 configured to stretch from a first average diameter 81
(as shown in FIGS. 6A, 6B, and 6D) to a second average diameter,
for example, up to a maximal average diameter 82 (FIG. 6C), greater
than tubular wall 72 outer diameter 73, when pressure P(78) inside
the tubular wall 72 distal portion 78 equals or exceeds a
predetermined expansion pressure Pdt. In some embodiments,
predetermined expansion pressure Pdt is greater than about 50 mm
Hg, or greater than about 80 mm Hg, or greater than about 100 mm
Hg, or greater than about 120 mm Hg, or higher, or lower, or an
intermediate value. In some embodiments, maximal average diameter
82 is equal to or higher than about 1 mm, or, equal to or higher
than about 2 mm, or, equal to or higher than about 4 mm, or, equal
to or higher than about 6 mm, or higher, or lower, or an
intermediate value.
[0092] In some embodiments, other portions of tubular wall 72 are
not subject for inflation under applicable pressures in intra-body
procedures, although in other embodiments, other infusion agent
flow disruption sections may be provided along or/and around
tubular wall 72, having similar or different expansion and
sensitivity parameters to infusion agent flow disruption section
80. In exemplary embodiments, infusion agent flow disruption
section 80 is further configured to collapse back to first average
diameter 81 when pressure P(78) is less than predetermined
expansion pressure Pdt. In exemplary embodiments, first average
diameter 81 substantially equals outer diameter 73 (as shown), or
is smaller therefrom.
[0093] A distal portion 78 of tubular wall 72 ends with a tip 79.
In exemplary embodiments, tip 79 is configured for suppressing flow
rate in a distal direction or/and to increase locally the pressure
P(78) in distal portion 78, distally to infusion agent flow
disruption section 80. Tip 79 may be shaped (e.g., narrowed, for
example, gradually, as shown, or as an orifice), accordingly, for
this purpose. In exemplary embodiments, tip 79 is configured to
maintain a pressure difference between internal pressure P(78) and
surrounding pressure P(84), at least within a chosen range of
pressure P(78). In some embodiments, a relief mechanism, for
example, a burst opening (e.g., burst slit), may be provided with
microcatheter 70, for example, adjacent to tip 79 or/and to
infusion agent flow disruption section 80 for allowing immediate
pressure drop in case the pressure P(78) in distal portion 78
increases above a maximally allowed value.
[0094] In some embodiments, infusion agent flow disruption section
80 allows continuous delivery of infusion agent 77 from reservoir
76 to tip 79 before, during, or/and after stretching or/and
collapsing thereof.
[0095] In some embodiments, infusion agent flow disruption section
80 includes an outer wall made of material(s), for example, being
thinner or/and more flexible than material(s) of other wall
portions of tubular wall 72. Materials may be of different types,
including metals, plastics, resilient materials, elastic material,
super-elastic material, or rigid materials. In some embodiments,
microcatheter 70 is configured as a single integrated structure,
wherein tubular wall 72 includes, and is structurally continuous
with, infusion agent flow disruption section 80 as a single member.
In alternative embodiments, infusion agent flow disruption section
80 is made, at least partially, as a separate part, and later
assembled with the entire outer wall 72 to form a single
microcatheter body.
[0096] In some embodiments, tubular wall 72 is configured for
delivery of an infusion suspension of an infusion agent (e.g.,
embolization material and/or contrast enhancing material) 77 from
reservoir 76 thru lumen 71 and tip 79 towards a target bodily part
(represented in this example by wall 84) in direct blood
communication with small blood vessel 83. Infusion agent delivery
occurs when internal pressure P(78) inside tubular wall 72 distal
portion 78 is less than predetermined expansion pressure Pdt and
greater than a first average ambient pressure developed between
tubular wall 72 distal portion 78 and target bodily part/wall 84
upon inserting tubular wall 72 in small blood vessel 83.
[0097] The infusion agent flow disruption section 80 is configured
such that upon elevation to a second average ambient pressure
within small blood vessel 83, being equal to or greater than
initial internal pressure P(78), upon accumulation of infusion
agent 77 between tip 79 and target bodily part/wall 84, the
pressure P(78) is increasable to a second inner pressure being
equal to or greater than predetermined expansion pressure Ptd,
whereby the infusion agent flow disruption section 80 stretches to
the second average diameter. In some embodiments, stretching stops
after occluding small blood vessel 83 or/and until a selected
pressure difference P(S) is developed between tubular wall distal
portion 78 and target bodily part/wall 84. In some embodiments,
microcatheter 70 is configured such that, under a selected third
inner pressure being greater than the first inner pressure and less
than the second inner pressure, infusion agent flow disruption
section 80 stretches in response to a systole and collapses in
response to a diastole, relative to the second average ambient
pressure.
[0098] In some embodiments, infusion agent flow disruption section
80 is configured to expand from first average diameter 81 to a
maximal second average diameter greater than inner diameter of
small blood vessel 83. In alternative embodiments, infusion agent
flow disruption section 80 is configured to expand to a maximal
second average diameter less than inner diameter of small blood
vessel 83.
[0099] In some embodiments, as shown in FIG. 6C, infusion agent
flow disruption section 80 is shaped, once expanded to maximal
average diameter 82 or/and to a diameter sized between outer
diameter 73 and maximal average diameter 82, to induce turbulent
flow in distal approximation thereto upon flowing (e.g., via back
flowing) of infusion agent 77 away from target bodily part 84 and
towards tip 79.
[0100] In some embodiments, infusion agent flow disruption section
is made from material being the same as that of the rest of tubular
wall 72. In exemplary embodiments, infusion agent flow disruption
section 80 is made of a material being impermeable to infusion
agent 77, such that when infusion agent flow disruption section 80
stretches to a second average diameter, the impermeable material
prevents passage and flowing (e.g., via back flowing) of the
infusion agent 77 therethrough.
[0101] FIG. 6A shows microcatheter 70 at initial stages of infusion
agent delivery, when the pressure difference P(84)-P(78) is
negative while pressure P(78) in distal portion 78 is substantially
lower than predetermined expansion pressure Pdt. FIG. 6B shows
microcatheter 70 at a higher pressure P(78) in distal portion 78,
yet still below predetermined expansion pressure Pdt, therefore
although the pressure difference may either be negative but small
in magnitude, null, or even positive, the infusion agent flow
disruption section 80 may still maintain the first average diameter
81. In FIG. 6C, pressure difference P(84)-P(78) is positive while
pressure source 75 elevates pressure P(78) to exceed predetermined
expansion pressure Pdt in a magnitude that causes infusion agent
flow disruption section 80 to stretch to maximal average diameter
82, preventing infusion agent 77 back flowing therethrough, for
example, while causing local turbulences which may decrease
pressure difference P(84)-P(78). FIG. 6D shows microcatheter 70
under a selected pressure difference P(S) where pressure P(78) in
distal portion 78 is less than predetermined expansion pressure
Pdt, therefore infusion agent flow disruption section 80 collapses
back to first average diameter 81.
[0102] In some embodiments, microcatheter 70 may be used in a
method for performing local embolization in a small blood vessel
feeding a cancerous target bodily part. In some embodiments. In
exemplary embodiments, the method may include at least one of the
following steps (not necessarily in same order). [0103] Providing
an embolization microcatheter, for example, microcatheter 70,
including a tubular wall having an outer diameter, enclosing a
single lumen extending therealong, and including a distal portion
ending with a tip opened to the lumen with a distal outlet, the
tubular wall distal portion includes an infusion agent flow
disruption section applicable via the lumen and configured to
disrupt passage around periphery of the distal portion of an
incoming retrograded flow of infusion agent, during a continuous
delivery of an infusion suspension of the infusion agent in an
infusion fluid through the lumen to the tip. [0104] Locating the
target bodily part and the small blood vessel using an imaging
technique. [0105] Providing a catheter in close proximity to a
proximal entry to the small blood vessel, the catheter includes a
hollow passage opened to the small blood vessel and has an inner
diameter equal to or less than 1 mm. [0106] Passing microcatheter
70 through the hollow passage and into the small blood vessel until
tip 79 is in a chosen distance from the target bodily part. [0107]
Applying pressure source 75, thereby delivering infusion agent
(e.g., embolization material and/or contrast enhancing material) 77
from reservoir 76 to the target bodily part. [0108] Accumulating
infusion agent 77 between the microcatheter tip 79 and the target
bodily part. [0109] Pressurizing lumen 71 so as to allow the
pressure P(78) inside tubular wall distal portion 78 to become
equal to or exceed the predetermined expansion pressure Pdt,
whereby infusion agent flow disruption section 80 stretches until
occluding the small blood vessel or/and until a selected pressure
difference P(S) is developed between the tubular wall distal
portion and the target bodily part.
[0110] Reference is now made to FIGS. 7A-7C, which schematically
illustrate side cut views of exemplary embodiments of a
microcatheter 90 in different scenarios, particularly highlighting
an exemplary infusion agent flow disruption section included in the
microcatheter tubular wall distal portion. Microcatheter 90
includes a single lumen 91 surrounded by a tubular wall 92 having
an outer diameter 93 and opened at both ends. In some embodiments,
tubular wall 92 is sized for unhindered insertion into a small
blood vessel 103, such as a celiac or hepatic artery. In some
embodiments, outer diameter 93 is equal to or less than about 2 mm,
or, equal to or less than about 1 mm. In some embodiments,
microcatheter 90 is measured as a 2.7 French catheter.
[0111] In some embodiments, tubular wall 92 is configured for
delivering infusion agent to a target bodily part such as a tumor
or cancerous tissue. A proximal portion of tubular wall 92 is
connectable to a reservoir and a pressure source (for example, as
shown in FIGS. 1B, 1C, 2A-2D) configured for containment and
delivery of infusion agent 97. Infusion agent 97 may include at
least one of liquid embolic agents (e.g., Onyx.TM. by Covidien,
n-butyle-2-cyanoacrylate, or ethiodized oil), sclerosing agents
(e.g., ethanol, ethanolamine oleate, or sodium tetradecyl sulfate),
or particulate embolic agents (e.g., hemostatic absorbable gelatin,
polyvinyl alcohol, or acrylic gelatin microspheres).
[0112] Distal portion 98 includes an infusion agent flow disruption
section 100 configured to stretch from a first average diameter 101
(FIG. 7A) to a second average diameter, for example, up to a
maximal average diameter 102 (FIGS. 7B and 7C), greater than
tubular wall 92 outer diameter 93, when pressure P(98) inside the
tubular wall 92 distal portion 98 equals or exceeds a predetermined
expansion pressure Pdt. In some embodiments, predetermined
expansion pressure Pdt is greater than about 50 mm Hg, or greater
than about 80 mm Hg, or greater than about 100 mm Hg, or greater
than about 120 mm Hg, or higher, or lower, or an intermediate
value. In some embodiments, maximal average diameter 102 is equal
to or greater than about 1 mm, or, equal to or greater than about 2
mm, or, equal to or greater than 4 mm, or, equal to or greater than
about 6 mm, or higher, or lower, or an intermediate value. In some
embodiments, other portions of tubular wall 92 are not subject for
inflation under applicable pressures in intra-body procedures,
although in other embodiments, other infusion agent flow disruption
sections may be provided along or/and around tubular wall 92,
having similar or different expansion and sensitivity parameters to
infusion agent flow disruption section 100. In exemplary
embodiments, infusion agent flow disruption section 100 is further
configured to collapse back to first average diameter 101 when
pressure P(98) is less than predetermined expansion pressure Pdt.
In exemplary embodiments, first average diameter 101 substantially
equals outer diameter 93 (as shown), or, is smaller or greater
therefrom.
[0113] A distal portion 98 of tubular wall 92 ends with a tip 99.
In exemplary embodiments, tip 99 is shaped (e.g., narrowed) in
order to maintain a pressure difference between internal pressure
P(98) and surrounding pressure P(104), at least within a chosen
range of pressure P(98). In some embodiments, and as shown,
infusion agent flow disruption section 100 includes tip 99.
[0114] In some embodiments, a relief mechanism (for example, a
burst opening for expelling fluid) may be provided with
microcatheter 90, for example, adjacent to tip 99 or/and to
infusion agent flow disruption section 100, for allowing immediate
pressure drop in case the pressure P(98) in distal portion 98
increases above a maximally allowed value. In some embodiments, and
as shown in FIG. 7C, infusion agent flow disruption section 100
includes a sub-section having at least one opening, for example,
opening 94, sized to allow passage therethrough of infusion agent
97 when infusion agent flow disruption section 100 is at least
partially stretched, or, for example, after infusion agent flow
disruption section 100 is fully stretched. Infusion agent flow
disruption section 100 may be configured such that the at least one
opening 94 is obstructed (such as by covering or elastic closure
95, shown in FIG. 7B) to prevent infusion agent 97 flowing
therethrough when infusion agent flow disruption section 100 is at
first average diameter 101, or, for example, at greater diameter,
such as maximal average diameter 102, yet below a predetermined
burst pressure Pbst. In exemplary embodiments, burst pressure Pbst
is substantially higher than predetermined expansion pressure Pdt,
for example, by at least about 20 mm Hg, or by at least about 50 mm
Hg, or higher, or lower, or an intermediate value. In some
embodiments, and as shown in FIG. 7C, infusion agent flow
disruption section 100 is configured such that the at least one
opening 94 is directed at least partially in a distal direction of
tubular wall 92 or/and towards tip 99, at least when opened (i.e.,
unobstructed).
[0115] In some embodiments, infusion agent flow disruption section
100 allows continuous delivery of infusion agent 97 from the
reservoir to tip 99 before, during, or/and after stretching or/and
collapsing thereof. In some such embodiments, when portion openings
94 are unobstructed, infusion agent 97 can be delivered
therethrough in parallel to delivery thru tip 99.
[0116] In some embodiments, infusion agent flow disruption section
100 includes an outer wall, for example, thinner or/and more
flexible than other wall portions of tubular wall 92. In some
embodiments, microcatheter 90 is configured as a single integrated
structure, wherein tubular wall 92 includes, and is structurally
continuous with, infusion agent flow disruption section 100 as a
single member. In alternative embodiments, infusion agent flow
disruption section 100 is made, at least partially, as a separate
part, and later assembled with the entire outer wall 92 to form a
single microcatheter body.
[0117] In some embodiments, tubular wall 92 is configured for
delivery of infusion agent 97 from a reservoir thru lumen 91 and
tip 99 (and, for example, thru the at least one opening 94) towards
a target bodily part (represented in this example by wall 104) in
direct blood communication with small blood vessel 103. Infusion
agent delivery occurs when internal pressure P(98) inside tubular
wall 92 distal portion 98 is less than predetermined expansion
pressure Pdt and greater than a first average ambient pressure
developed between tubular wall 92 distal portion 98 and target
bodily part/wall 104 upon inserting tubular wall 92 in small blood
vessel 103.
[0118] The infusion agent flow disruption section 100 is configured
such that upon elevation to a second average ambient pressure
within small blood vessel 103, being equal to or greater than
initial internal pressure P(98), upon accumulation of infusion
agent 97 between tip 99 and target bodily part/wall 104, the
pressure P(98) is increasable to a second inner pressure being
equal to or greater than predetermined expansion pressure Ptd,
whereby infusion agent flow disruption section 100 stretches (for
example, as shown in FIG. 7B). In some embodiments, stretching
stops after occluding small blood vessel 103 or/and until a
selected pressure difference is developed between tubular wall
distal portion 98 and target bodily part/wall 104. In some
embodiments, microcatheter 90 is configured such that, under a
selected third inner pressure being greater than the first inner
pressure and less than the second inner pressure, infusion agent
flow disruption section 100 stretches in response to a systole and
collapses in response to a diastole, relative to the second average
ambient pressure.
[0119] In some embodiments, infusion agent flow disruption section
100 is configured to expand from first average diameter 101 to a
maximal second average diameter greater than inner diameter of
small blood vessel 103. In alternative embodiments, infusion agent
flow disruption section 100 is configured to expand to a maximal
second average diameter less than inner diameter of small blood
vessel 103.
[0120] In some embodiments, infusion agent flow disruption section
100 is shaped, once expanded to maximal average diameter 102 or/and
to a diameter sized between outer diameter 93 and maximal average
diameter 102, to induce turbulent flow in distal approximation
thereto upon flowing (e.g., via back flowing) of infusion agent 97
away from target bodily part 104 and towards tip 99.
[0121] FIGS. 8A-8B schematically illustrate partial side cut views
of exemplary embodiments of a portion of an infusion agent flow
disruption section 111 (in exemplary microcatheter 110) that
includes a valve mechanism 112, before (FIG. 8A) and after (FIG.
8B) actuation thereof. Microcatheter 110 may be an embolization
microcatheter sized and configured for delivering infusion agent
(e.g., embolization material and/or contrast enhancing material)
113 (e.g., in the form of beads) in a small blood vessel towards a
target bodily part. Microcatheter 110 includes a lumen 114
surrounded by a tubular wall 115 having an outer diameter and
opened at both ends. In some embodiments, tubular wall 115 is sized
for unhindered insertion into a small blood vessel, such as a
celiac or hepatic artery. In some embodiments, outer diameter of
microcatheter 110 is equal to or less than about 2 mm, or, equal to
or less than about 1 mm. In some embodiments, microcatheter 110 has
an external diameter equal to the diameter of a commercially
available microcatheter, such as a 2.1 French catheter, a 2.7
French catheter, or a 2.9 French catheter.
[0122] Infusion agent 113 may include at least one of liquid
embolic agents (e.g., Onyx.TM. by Covidien,
n-butyle-2-cyanoacrylate, or ethiodized oil), sclerosing agents
(e.g., ethanol, ethanolamine oleate, or sodium tetradecyl sulfate),
or particulate embolic agents (e.g., hemostatic absorbable gelatin,
polyvinyl alcohol (PVA), acrylic gelatin microspheres, or glass).
In exemplary embodiments, infusion agent 113 is of particulate form
(e.g., non-spherical particles, or microspheres) having an average
size (long dimension or diameter) in a range of between about 25
microns (.mu.m) and about 1,500 microns (.mu.). In exemplary
embodiments, infusion agent 113 has a compressibility in a range of
between about 10% and about 40%. For example, polyvinyl alcohol
(PVA) type infusion agent has a compressibility in a range of
between about 20% and about 30%.
[0123] Infusion agent flow disruption section 111 is configured to
disrupt passage of an incoming retrograded flow 119 of the infusion
agent around outer periphery of tubular wall 115 distal end
adjacent thereto, during continuous delivery of infusion agent 113
through distal outlet of microcatheter 110. Flow disruption section
111 is configured to diminish, block, or/and cause turbulence or
vortex in, incoming retrograded flow 119 of the infusion agent,
optionally increasing local pressure thereabout.
[0124] Flow disruption section 111 includes a plurality of (side)
openings 116 distributed around or/and along it, each opening is
shaped or/and sized to allow passage therethrough of an infusion
fluid 117, and to block passage therethrough of the infusion agent
113.
[0125] Infusion fluid 117, in exemplary embodiments, includes a
contrast enhancing agent, for example, diluted to a certain degree
such as by saline. In some instances, the medical practitioner may
mix together a viscous contrast enhancing media with infusion
agent, for example, embolization material including saline and
embolization beads, for example, in a volumetric ratio of 50:50,
thereby producing a viscous fluidic infusion suspension of
embolization beads and contrast enhancing media diluted to a chosen
degree. In exemplary embodiments, the contrast enhancing material
(agent) (such as contrast enhancing material (agent) CM shown in
FIG. 1A) may be, or include, any of various different types or
kinds of contrast media, for example, Visipaque.TM. (iodixanol), or
Omnipaque.TM. (iohexol), among many other suitable types and kinds
of contrast media.
[0126] One or more opening 116 includes a pore having a cross
sectional dimension less than minimal diameter of the infusion
agent embolization material (e.g., bead diameter). Such cross
sectional dimension is, for example, less than about 500 microns
(.mu.m), or, equal to or less than about 100 microns (.mu.m), or,
equal to or less than about 40 microns (.mu.m). In exemplary
embodiments, the cross section dimension is in a range of between
about 20 microns (.mu.m) and about 30 microns (.mu.m), for example,
about 28 microns (.mu.m). For example, as shown, each pore is
located at end of a channel being angled relative to a long axis of
lumen 114 or/and relative to a radial axis thereof at a cross
section adjacent thereto. In exemplary embodiments, at least two
pores are angularly located in different directions such that a
first stream of the infusion suspension in immediate vicinity of a
first pore at least partially intersects a second stream of the
infusion suspension in immediate vicinity of a second pore.
[0127] In some embodiments, lumen 114 is configured to deliver a
suspension of infusion fluid 117 and infusion agent 113 (e.g., in a
form of beads). In some embodiments, a distal outlet of
microcatheter 110 is shaped or/and sized to allow passage
therethrough of the suspension of infusion fluid 117 and the beads
113, and at least one of side opening 116 is shaped or/and sized to
allow passage therethrough of infusion fluid 117, and to block
passage therethrough of most or all beads 113, for example if at
least one cross sectional dimension (e.g., length, width, diameter)
of the pore in this at least one opening is less than a minimal
diameter of the beads.
[0128] In some embodiments, each side opening 116 is shaped or/and
sized to allow passage therethrough of infusion fluid 117, and to
block passage therethrough of beads 113, during flow of the
infusion suspension through the distal outlet. In some other
embodiments, each side opening 116 is shaped or/and sized to allow
passage therethrough of infusion fluid 117, and to block passage
therethrough of beads 113, during conditions when the infusion
suspension is blocked or interrupted from flowing through the
distal outlet.
[0129] In some embodiments, a total opened cross section of all
side openings 116 is equal to or greater than a smallest cross
section of lumen 114 and the distal outlet.
[0130] In some embodiments, infusion fluid 117 at normal body
temperature has an average viscosity of at least about 0.8 mPas, or
at least about 5 mPas, or at least about 10 mPas, or at least about
20 mPas. In exemplary embodiments, infusion fluid 117 is
pre-heated, for example, to a temperature higher than about
37.degree. C., before reaching tubular wall 115 distal portion in
lumen 114.
[0131] In some embodiments, a farthest distal side opening 116 is
located within a range of between about 0 mm and about 20 mm, or
within a range of between about 0 mm and about 10 mm, or within a
range of between about 0 mm and about 5 mm, proximally to the
distal outlet.
[0132] Valve mechanism 112 is configured to cover side openings 116
when pressure inside tubular wall 115 distal portion is less than a
predetermined pressure, and to uncover side openings 116 when
pressure inside the tubular wall distal portion is greater than the
predetermined pressure. Internal pressure may be built using an
orifice or a narrowing (as shown in FIGS. 6A-6D, for example) at
the distal outlet. In some embodiments, valve mechanism 112
includes a cover 118 configured to cover the plurality of side
openings 116 and to prevent passage therethrough of fluids, and
configured to uncover the plurality of side openings 116 when
tubular wall 115 section is immersed in a proximally flowing fluid,
such as for example, when it is provided in the small blood vessel
when retrograded flow occurs. The tubular wall section 115 may
include a space between the plurality of side openings 116 and
cover 118, which is sized to accumulate a predetermined maximal
volume of infusion fluid 117 absent of beads 113. Such
predetermined maximal volume may be in a range of between about 0
ml and about 1 ml. In exemplary embodiments, the predetermined
maximal volume is at least about 1 ml, or at least about 5 ml, or
at least about 10 ml.
[0133] Cover 118 may be fabricated from metal, for example, a
super-elastic metal alloy (e.g., nitinol or stainless steel), or
from a polymer (e.g., PTFE, ePTFE, polyester, FEP, urethane, Pebax,
or Pellethane) for example, rigid or semi-rigid. In some
embodiments, cover 118 may increase the overall microcatheter
diameter by an amount between about 0.5 mm and about 1 mm, for
example, about 0.8 mm, when cover 118 is in a closed position. In
some embodiments, cover 118 may increase the overall microcatheter
diameter by an amount between about 1 mm and about 10 mm, for
example, by about 5 mm, when cover 118 is in an opened position. In
exemplary embodiments, cover 118 has a length in a range of between
about 1 mm and about 5 m. In exemplary embodiments, cover 118 has a
thickness in a range of between about 20 microns and about 500
microns. In exemplary embodiments, cover 118 is attached to tubular
wall 115 via at least one of: laser cut hinges, gluing, melting,
and heat shrinking of an outer layer.
[0134] FIGS. 9A-9B schematically illustrate side cut views of
exemplary embodiments of a distal end of an exemplary microcatheter
120, particularly showing an exemplary embodiment of a valve
mechanism 121 configured to cover (FIG. 9A) and uncover (FIG. 9B)
side openings 122 provided at an infusion agent flow disruption
section 123. Microcatheter 120 may be an embolization microcatheter
sized and configured for delivering infusion agent 124 (e.g., in
the form of beads) in a small blood vessel towards a target bodily
part. Microcatheter 120 includes a lumen 125 surrounded by a
tubular wall 126 having an outer diameter and opened at both ends.
In some embodiments, tubular wall 126 is sized for unhindered
insertion into a small blood vessel, such as a celiac or hepatic
artery. In some embodiments, outer diameter of microcatheter 120 is
equal to or less than about 2 mm, or, equal to or less than about 1
mm. In some embodiments, microcatheter 120 has an external diameter
equal to the diameter of a commercially available microcatheter,
such as a 2.1 French catheter, a 2.7 French catheter, or a 2.9
French catheter.
[0135] Infusion agent 124 may include at least one of liquid
embolic agents (e.g., Onyx.TM. by Covidien,
n-butyle-2-cyanoacrylate, or ethiodized oil), sclerosing agents
(e.g., ethanol, ethanolamine oleate, or sodium tetradecyl sulfate),
or particulate embolic agents (e.g., hemostatic absorbable gelatin,
polyvinyl alcohol, or acrylic gelatin microspheres). In exemplary
embodiments, infusion agent 124 is of particulate form (e.g.,
non-spherical particles, or microspheres) having an average size
(long dimension or diameter) in a range of between about 30 microns
(.mu.) and about 1500 microns (.mu.). In exemplary embodiments,
infusion agent 124 has a compressibility in a range of between
about 10% and about 40%. For example, polyvinyl alcohol (PVA) type
infusion agent has a compressibility in a range of between about
20% and about 30%.
[0136] Infusion agent flow disruption section 123 is configured to
disrupt passage therethrough of an incoming retrograded flow 127 of
infusion agent, during continuous delivery of infusion agent 124
through distal outlet of microcatheter 120. Flow disruption section
123 is configured to block, or/and cause turbulence in, incoming
retrograded flow 127 of the infusion agent, thereby increasing
local pressure thereabout.
[0137] (Side) openings 122 are distributed around or/and along flow
disruption section 123, each opening is shaped or/and sized to
allow passage therethrough of an infusion fluid 128, and to block
passage therethrough of the infusion agent 124.
[0138] Infusion fluid 128, in exemplary embodiments, includes a
contrast enhancing agent, for example, diluted to a certain degree
such as by saline. In some instances, the medical practitioner may
mix together a viscous contrast enhancing media with infusion agent
including saline and embolization beads, for example, in a
volumetric ratio of 50:50, thereby producing a viscous fluidic
infusion suspension of embolization beads and contrast enhancing
media diluted to a chosen degree. In exemplary embodiments, the
contrast enhancing material (agent) (such as contrast enhancing
material (agent) CM shown in FIG. 1A) may be, or include, any of
various different types or kinds of contrast media, for example,
Visipaque.TM. (iodixanol), or Omnipaque.TM. (iohexol), among many
other suitable types and kinds of contrast media.
[0139] One or more opening 122 includes a pore or/and slits having
a cross sectional dimension less than minimal diameter of the
infusion agent (e.g., beads diameter). Such cross sectional
dimension is, for example, less than about 500 microns (.mu.m), or,
equal to or less than about 100 microns (.mu.m), or, equal to or
less than about 40 microns (.mu.m). In exemplary embodiments, the
cross sectional dimension is in a range of between about 20 microns
(.mu.m) and about 30 microns (.mu.m), for example, about 28 microns
(.mu.m). For example, as shown, each pore is located at end of a
channel being angled relative to a long axis of lumen 125 or/and
relative to a radial axis thereof at a cross section adjacent
thereto. In exemplary embodiments, at least two pores are angularly
located in different directions such that a first stream of the
infusion fluid in immediate vicinity of a first pore at least
partially intersects a second stream of the infusion fluid in
immediate vicinity of a second pore.
[0140] In some embodiments, lumen 125 is configured to deliver a
suspension of infusion fluid 128 and infusion agent 124 (e.g., in a
form of beads). In some embodiments, a distal outlet 129 of
microcatheter 120 is shaped or/and sized to allow passage
therethrough of the infusion suspension of infusion fluid 128 and
the beads 124, and each side opening 122 is shaped or/and sized to
allow passage therethrough of infusion fluid 128, and to block
passage therethrough of beads 124, for example if a cross sectional
dimension of the pore in each opening is less than a minimal
diameter of the beads.
[0141] In some embodiments, each side opening 122 is shaped or/and
sized to allow passage therethrough of infusion fluid 128, and to
block passage therethrough of beads 124, during flow of the
suspension through distal outlet 129. In some other embodiments,
each side opening 122 is shaped or/and sized to allow passage
therethrough of infusion fluid 128, and to block passage
therethrough of beads 124, during conditions when the infusion
suspension is blocked or interrupted from flowing through distal
outlet 129.
[0142] In some embodiments, a total opened cross section of all
side openings 122 is equal to or greater than a smallest cross
section of lumen 125 and distal outlet 129.
[0143] In some embodiments, infusion fluid 128 at normal body
temperature has an average viscosity of at least about 0.8 mPas, or
at least about 5 mPas, or at least about 10 mPas, or at least about
20 mPas. In exemplary embodiments, infusion fluid 128 is
pre-heated, for example, to a temperature higher than about
37.degree. C., before reaching tubular wall 126 distal portion in
lumen 125.
[0144] In some embodiments, a farthest distal side opening 122 is
located within a range of between about 0 mm and about 20 mm, or
within a range of between about 0 mm and about 10 mm, or within a
range of between about 0 mm and about 5 mm, proximally to the
distal outlet.
[0145] Valve mechanism 121 is configured to cover side openings 122
when pressure inside tubular wall 126 distal portion is less than a
predetermined pressure, and to uncover side openings 122 when
pressure inside tubular wall distal portion is greater than the
predetermined pressure. Internal pressure may be built using an
orifice or a narrowing (as shown in FIGS. 6A-6D, for example) at
distal outlet 129. Valve mechanism 121 may include a
normally-withdrawn pop-out cover 130, for example, connected to a
tension spring, configured to fully withdraw into tubular wall 126
(FIG. 9A) at an internal pressure less than the predetermined
pressure and to at least partially protrude at an internal pressure
exceeding the predetermined pressure. Valve mechanism 121 may also
be configured for extending cover 130 in order to distance distal
outlet 129 away from side openings 122.
[0146] FIGS. 10A-10B schematically illustrate side cut views
representing possible scenarios of implementing exemplary
embodiments of a method for performing local embolization in a
small blood vessel SBV feeding a (for example, cancerous) target
bodily part TBP. Such exemplary embodiments include detecting an
indication of presence of infusion fluid in a blood vessel portion
BVP upstream to small blood vessel SBV. A microcatheter 170 which
may be used in this method, configured for positioning and
delivering infusion agent (e.g., embolization material and/or
contrast enhancing material) in small blood vessel SBV, includes a
lumen configured to deliver an infusion suspension of an infusion
fluid 171 and infusion agent 172 (e.g., in a form of beads), the
lumen is surrounded by a tubular wall 173 having an outer diameter
and opened at both ends. In some embodiments, infusion fluid 171
includes a contrast enhancing agent, so it can be detected under
x-ray imaging. A distal portion of tubular wall 173 ends with a tip
174 enclosing a distal outlet 175. At least one side opening 176,
having a total opened cross section, is, for example, positioned
or/and distributed around or/and along a section of tubular wall
173 proximally to distal outlet 175. Distal outlet 175 is shaped
or/and sized to allow passage therethrough of the infusion
suspension of infusion fluid 171 and beads 172, and each side
opening 176 is shaped or/and sized to allow passage therethrough of
infusion fluid 171, and to block passage therethrough of beads
172.
[0147] Microcatheter 170 is passed into small blood vessel SBV
until tip 174 is in a chosen distance to target bodily part TBP.
The infusion suspension of infusion fluid 171 and beads 172 may
then be delivered via distal outlet 175 towards target bodily part
TBP. Before, after or in parallel to infusion suspension delivery,
a volume of infusion fluid 171 is infused through side openings 176
while beads 172 are blocked from passing therethrough, as shown in
FIG. 10A.
[0148] In some embodiments, the infusing occurs following blood
flow reflux from the small blood vessel SBV towards blood vessel
portion BVP (FIG. 10B). Blood vessel portion BVP is selected, being
upstream to small blood vessel SBV, and is then monitored using an
imaging technique. In some embodiments, x-ray (e.g., fluoroscopy),
ultrasound or/and Doppler techniques are used for the monitoring,
thus blood vessel portion BVP is chosen also based on ease or/and
feasibility of applying any of these techniques, accordingly. Via
monitoring, the medical practitioner may seek to detect an
indication of presence of infusion fluid 171 in blood vessel
portion BVP so, in response, he may stop any further delivery of
infusion suspension.
[0149] In exemplary embodiments, blood vessel portion BVP distance
from small blood vessel SBV is determined with a (e.g.,
predetermined) minimal effectively imaged quantity of infusion
fluid 171 volume, originating from side openings 176, flowing into
blood vessel portion BVP before the suspension, which originates
from distal outlet 175, reaches blood vessel portion BVP following
blood flow reflux from small blood vessel SBV towards blood vessel
portion BVP. The required distance may be up to about 10 mm, or at
least about 10 mm, or at least about 20 mm, or at least about 50
mm.
[0150] Each of the following terms written in singular grammatical
form: `a`, `an`, and `the`, as used herein, means `at least one`,
or `one or more`. Use of the phrase `one or more` herein does not
alter this intended meaning of `a`, `an`, or `the`. Accordingly,
the terms `a`, `an`, and `the`, as used herein, may also refer to,
and encompass, a plurality of the stated entity or object, unless
otherwise specifically defined or stated herein, or, unless the
context clearly dictates otherwise. For example, the phrases: `a
unit`, `a device`, `an assembly`, `a mechanism`, `a component`, `an
element`, and `a step or procedure`, as used herein, may also refer
to, and encompass, a plurality of units, a plurality of devices, a
plurality of assemblies, a plurality of mechanisms, a plurality of
components, a plurality of elements, and, a plurality of steps or
procedures, respectively.
[0151] Each of the following terms: `includes`, `including`, `has`,
`having`, `comprises`, and `comprising`, and, their
linguistic/grammatical variants, derivatives, or/and conjugates, as
used herein, means `including, but not limited to`, and is to be
taken as specifying the stated component(s), feature(s),
characteristic(s), parameter(s), integer(s), or step(s), and does
not preclude addition of one or more additional component(s),
feature(s), characteristic(s), parameter(s), integer(s), step(s),
or groups thereof. Each of these terms is considered equivalent in
meaning to the phrase `consisting essentially of`.
[0152] Each of the phrases `consisting of` and `consists of`, as
used herein, means `including and limited to`.
[0153] The phrase `consisting essentially of`, as used herein,
means that the stated entity or item (system, system unit, system
sub-unit, device, assembly, sub-assembly, mechanism, structure,
component, element, or, peripheral equipment, utility, accessory,
or material, method or process, step or procedure, sub-step or
sub-procedure), which is an entirety or part of an exemplary
embodiment of the disclosed invention, or/and which is used for
implementing an exemplary embodiment of the disclosed invention,
may include at least one additional `feature or characteristic`
being a system unit, system sub-unit, device, assembly,
sub-assembly, mechanism, structure, component, or element, or,
peripheral equipment, utility, accessory, or material, step or
procedure, sub-step or sub-procedure), but only if each such
additional `feature or characteristic` does not materially alter
the basic novel and inventive characteristics or special technical
features, of the claimed entity or item.
[0154] The term `method`, as used herein, refers to steps,
procedures, manners, means, or/and techniques, for accomplishing a
given task including, but not limited to, those steps, procedures,
manners, means, or/and techniques, either known to, or readily
developed from known steps, procedures, manners, means, or/and
techniques, by practitioners in the relevant field(s) of the
disclosed invention.
[0155] Throughout this disclosure, a numerical value of a
parameter, feature, characteristic, object, or dimension, may be
stated or described in terms of a numerical range format. Such a
numerical range format, as used herein, illustrates implementation
of some exemplary embodiments of the invention, and does not
inflexibly limit the scope of the exemplary embodiments of the
invention. Accordingly, a stated or described numerical range also
refers to, and encompasses, all possible sub-ranges and individual
numerical values (where a numerical value may be expressed as a
whole, integral, or fractional number) within that stated or
described numerical range. For example, a stated or described
numerical range `from 1 to 6` also refers to, and encompasses, all
possible sub-ranges, such as `from 1 to 3`, `from 1 to 4`, `from 1
to 5`, `from 2 to 4`, `from 2 to 6`, `from 3 to 6`, etc., and
individual numerical values, such as `1`, `1.3`, `2`, `2.8`, `3`,
`3.5`, `4`, `4.6`, `5`, `5.2`, and `6`, within the stated or
described numerical range of `from 1 to 6`. This applies regardless
of the numerical breadth, extent, or size, of the stated or
described numerical range.
[0156] Moreover, for stating or describing a numerical range, the
phrase `in a range of between about a first numerical value and
about a second numerical value`, is considered equivalent to, and
meaning the same as, the phrase `in a range of from about a first
numerical value to about a second numerical value`, and, thus, the
two equivalently meaning phrases may be used interchangeably.
[0157] The term `about`, as used herein, refers to .+-.10% of the
stated numerical value.
[0158] It is to be fully understood that certain aspects,
characteristics, and features, of the invention, which are, for
clarity, illustratively described and presented in the context or
format of a plurality of separate embodiments, may also be
illustratively described and presented in any suitable combination
or sub-combination in the context or format of a single embodiment.
Conversely, various aspects, characteristics, and features, of the
invention which are illustratively described and presented in
combination or sub-combination in the context or format of a single
embodiment, may also be illustratively described and presented in
the context or format of a plurality of separate embodiments.
[0159] Although the invention has been described in conjunction
with specific embodiments thereof, it is evident that many
alternatives, modifications and variations will be apparent to
those skilled in the art. Accordingly, it is intended to embrace
all such alternatives, modifications and variations that fall
within the spirit and broad scope of the appended claims.
[0160] All publications, patents and patent applications mentioned
in this specification are herein incorporated in their entirety by
reference into the specification, to the same extent as if each
individual publication, patent or patent application was
specifically and individually indicated to be incorporated herein
by reference. In addition, citation or identification of any
reference in this application shall not be construed as an
admission that such reference is available as prior art to the
present invention. To the extent that section headings are used,
they should not be construed as necessarily limiting.
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