U.S. patent application number 13/726105 was filed with the patent office on 2013-08-15 for method and apparatus for treatment of intracranial hemorrhages.
This patent application is currently assigned to EKOS CORPORATION. The applicant listed for this patent is EKOS Corporation. Invention is credited to Ronald L. Haas, Robert L. Wilcox.
Application Number | 20130211316 13/726105 |
Document ID | / |
Family ID | 39832572 |
Filed Date | 2013-08-15 |
United States Patent
Application |
20130211316 |
Kind Code |
A1 |
Wilcox; Robert L. ; et
al. |
August 15, 2013 |
METHOD AND APPARATUS FOR TREATMENT OF INTRACRANIAL HEMORRHAGES
Abstract
An ultrasound catheter with fluid delivery lumens, fluid
evacuation lumens and a light source is used for the treatment of
intracerebral hemorrhages. After the catheter is inserted into a
blood clot in the brain, a lytic drug can be delivered to the blood
clot via the fluid delivery lumens while applying ultrasonic energy
to the treatment site. As the blood clot is dissolved, the
liquefied blood clot can be removed by evacuation through the fluid
evacuation lumens.
Inventors: |
Wilcox; Robert L.; (Bothell,
WA) ; Haas; Ronald L.; (Kirkland, WA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
EKOS Corporation; |
|
|
US |
|
|
Assignee: |
EKOS CORPORATION
Bothell
WA
|
Family ID: |
39832572 |
Appl. No.: |
13/726105 |
Filed: |
December 22, 2012 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
12143470 |
Jun 20, 2008 |
|
|
|
13726105 |
|
|
|
|
60945846 |
Jun 22, 2007 |
|
|
|
61032741 |
Feb 29, 2008 |
|
|
|
Current U.S.
Class: |
604/22 |
Current CPC
Class: |
A61B 18/24 20130101;
A61M 2025/0002 20130101; A61M 25/00 20130101; A61B 2090/306
20160201; A61B 2217/005 20130101; A61B 2017/12004 20130101; A61B
2217/007 20130101; A61M 25/007 20130101; A61B 2017/00084 20130101;
A61M 1/0084 20130101; A61M 25/0032 20130101; A61M 25/003 20130101;
A61B 2090/309 20160201; A61B 2090/064 20160201; A61B 2017/00561
20130101; A61B 17/2202 20130101; A61M 2205/058 20130101 |
Class at
Publication: |
604/22 |
International
Class: |
A61M 25/00 20060101
A61M025/00 |
Claims
1. A method for treating a blood clot resulting from an
intracranial hemorrhage comprising: forming a hole in a patient's
skull; positioning at least a portion of a treatment portion of a
catheter of into the blood clot; delivering a therapeutic compound
to the blood clot through a fluid delivery lumen in the catheter;
activating an ultrasound element in a treatment portion of the
catheter; and evacuating a fluid around the treatment portion into
the elongate tubular body.
2. The method of claim 1, wherein the therapeutic compound is a
thrombolytic compound.
3. The method of claim 1, wherein the catheter comprises an
external ventricular drainage catheter.
4. The method of claim 3, further comprising inserting an
ultrasound catheter into the external ventricular drainage
catheter.
5. The method of claim 3, further comprising inserting an
ultrasound catheter alongside the external ventricular drainage
catheter.
6. The method of claim 3, wherein the activating an ultrasound
element in a treatment portion of the catheter comprising
activating ultrasound radiating members incorporated in to external
ventricular drainage catheter.
7. The method of claim 1, further comprising measuring the pressure
within the treatment portion of the catheter with a pressure sensor
located within the treatment portion.
8. The method of claim 1, wherein the treatment catheter is
positioned within the blood clot with fluoroscopic, magnetic
resonance, neuronavigation, and/or computed tomography
visualization.
9. The method of claim 1, wherein the positioning the at least
portion of a treatment portion of an catheter into the blood clot
comprises positioning the catheter extravascularly.
10. A method for treating a blood clot in a patient comprising:
advancing a ultrasound catheter into an external ventricular
drainage (EVD) catheter; and transmitting ultrasound energy with
the ultrasound catheter.
11. The method of claim 10, further comprising delivering a fluid
comprising a thrombolytic drug into the external ventricular
drainage (EVD).
12. The method of claim 10, comprising transmitting ultrasound
energy at a frequency between about 20 kHz and about 20 MHz.
13. The method of claim 12, wherein a blood clot is positioned
outside the external ventricular drainage (EVD) catheter.
14. The method of claim 12, wherein the ultrasound radiating member
is incorporated in to external ventricular drainage catheter.
15. A method for treating a blood clot in a patient comprising:
forming a hole in a patient's skull; advancing an external
ventricular drainage (EVD) catheter through the hole to into a
target in a patient's brain; advancing a ultrasound catheter into
the external ventricular drainage (EVD) catheter; and transmitting
ultrasound energy from the ultrasound catheter.
16. The method of claim 15, comprising transmitting ultrasound
energy at a frequency between about 20 kHz and about 20 MHz.
17. The method of claim 16 wherein the hole is a burr hole.
18. The method of claim 16, further comprising inserting the
external ventricular drainage (EVD) catheter into an introducer
sheath.
19. The method of claim 16, wherein the external ventricular
drainage (EVD) catheter is advanced into the ventricles of the
patient's brain.
20. The method of claim 16, further comprising inserting the
ultrasound catheter through a proximal end of the external
ventricular drainage (EVD) catheter.
21. The method of claim 16, further comprising delivering a
therapeutic compound to the external ventricular drainage (EVD)
catheter.
22. The method of claim 21, wherein the therapeutic compound is a
thrombolytic compound.
23. The method of claim 16, wherein the ultrasound catheter has
multiple ultrasound elements.
24. The method of claim 16, wherein clot outside the wherein the
external ventricular drainage (EVD) is dissolved.
25. The method of claim 24, withdrawing the dissolved blood clot
through the external ventricular drainage (EVD) is dissolved.
26. The method of claim 16, wherein an ultrasound radiating member
of the ultrasound catheter extends past a distal tip of the
external ventricular drainage (EVD) catheter.
27. The method of claim 15, wherein the external ventricular
drainage (EVD) catheter is positioned within the blood clot with
fluoroscopic, magnetic resonance, neuronavigation, and/or computed
tomography visualization.
28. The method of claim 15, wherein a stylet positioned in the
external ventricular drainage (EVD) when advancing an external
ventricular drainage (EVD) catheter into the patient's brain.
29. The method of claim 24, further comprising removing the
stylet.
30. The method of claim 15, wherein the target is a blood clot.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This is a continuation of U.S. patent application Ser. No.
12/143,470, filed Jun. 20, 2009, which claims the priority benefit
of U.S. Provisional Application No. 60/945,846, filed Jun. 22,
2007, and U.S. Provisional Application No. 61/032,741, filed Feb.
29, 2008, the entire contents of these applications are hereby
incorporated by reference herein.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates generally to the treatment of
intracranial hemorrhages, and more specifically, to the treatment
of intracranial hemorrhages using an ultrasound catheter.
[0004] 2. Background of the Invention
[0005] Up to 70,000 Americans each year suffer a hemorrhagic
stroke. Most of these occur in the basal ganglia, and a third of
those include bleeding into the ventricles. Half of these victims
will die within months, and a quarter of the survivors will have a
second stroke within five years.
[0006] Bleeding in the brain occurs due to high blood pressure,
aneurysms, and less frequently arterio-venous malformations (AVM),
and increases in incidence with age. Factors including smoking,
diabetes, and obesity play roles, as do amyloid deposits in the
elderly.
[0007] With respect to stroke treatment, up to 7,000 cases per year
involve surgical intervention. The objectives of surgical
intervention generally include clipping bleeding aneurysms,
removing bleeding AVMs, and removing clot volume in intracranial
hemorrhages (ICH).
[0008] In certain applications, an interventional radiologist will
insert Goldvalve detachable balloons, Guglielmi detachable coils,
or Onyx liquid embolic to occlude AVMs and saccular aneurysm. These
applications are primarily preventive (e.g., preventing a second
bleed). Other methods of reducing further bleeding include using
embolics and FVIIa, and/or maintaining intracranial pressure below
mean arterial pressure. Medical therapy typically also includes
head elevation, Tylenol for temperature reduction, paralytics to
prevent coughing, intubation to prevent aspiration, Mannitol and
diuretics to reduce fluid volume, and seizure preventatives.
[0009] Recently, lytics have been considered as a treatment option
to remove obstruction in the ventricles and to reduce intracranial
pressure. However, such lytic treatment has not been widely adopted
because it is generally considered too slow to provide sufficient
clinical benefits.
[0010] Accordingly, it would be desirable to provide a method and
apparatus for rapidly reducing the volume of the blood clot in the
patient's brain.
SUMMARY OF THE INVENTION
[0011] An embodiment of an ultrasound catheter for treatment of a
blood clot resulting from an intracranial hemorrhage comprise an
elongate tubular body having a distal portion, a proximal portion
and a central lumen. The catheter further comprises a plurality of
ultrasound radiating members positioned within the tubular body. A
first fluid delivery lumen is formed within the elongate tubular
body. The first fluid delivery lumen includes a first fluid
delivery port located on a first region of the distal portion of
the elongate tubular body and is configured to allow a fluid to
flow from within the first fluid delivery lumen to the blood clot.
In addition, a first fluid evacuation lumen is formed within the
elongate tubular body. The first fluid evacuation lumen includes a
first fluid evacuation port located on a second region of the
distal portion of the elongate tubular body and is configured to
allow a fluid to flow into the first fluid evacuation lumen.
[0012] In some embodiments, the ultrasound catheter further
comprises a light source located with the ultrasound assembly. The
ultrasound catheter can also have a second fluid delivery lumen
formed within the elongate tubular body. The second fluid delivery
lumen includes a second fluid delivery port located on a third
region of the distal region of the elongate tubular body adjacent
to the first region and is configured to allow a fluid to flow from
within the second fluid delivery lumen to the blood clot.
[0013] In some embodiments, the ultrasound catheter further
comprises a slidable sealing surface located on the proximal
portion of the elongate tubular body.
[0014] In some embodiments, the ultrasound catheter further
comprises a temperature sensor located within the distal portion of
the elongate tubular body.
[0015] In some embodiments, the ultrasound catheter further
comprises a pressure sensor located within the distal portion
elongate tubular body. In some embodiments, the pressure sensor is
located within the first fluid delivery lumen proximate the first
fluid delivery port. In some embodiments, the pressure sensor is
located within the first fluid evacuation lumen proximate the first
fluid evacuation port.
[0016] An embodiment of a method for treating a blood clot
resulting from an intracranial hemorrhage comprises positioning at
least a portion of the distal portion of the elongate tubular body
of the ultrasound catheter of claim 1 into the blood clot,
activating the ultrasound assembly, delivering a lytic drug to the
blood clot through the first fluid delivery lumen and evacuating a
fluid around the distal portion of the elongate tubular body into
the first fluid evacuation lumen.
[0017] In some embodiments, the method further comprises activating
a light source located with the ultrasound assembly.
[0018] In some embodiments, the method further comprises sliding a
slidable sealing surface located on the proximal portion of the
enlongate tubular body towards the distal portion of the enlongate
tubular body.
[0019] In some embodiments, the method further comprises measuring
the temperature within a portion of the elongate tubular body with
a temperature sensor located within the distal portion of the
elongate tubular body.
[0020] In some embodiments, the method further comprises measuring
the pressure within a portion of the elongate tubular body with a
pressure sensor located within the distal portion of the elongate
tubular body. In some embodiments, the pressure sensor is located
within the first fluid delivery lumen proximate the first fluid
delivery port. In some embodiments, the pressure sensor is located
within the first fluid evacuation lumen proximate the first fluid
evacuation port.
BRIEF DESCRIPTION OF THE DRAWINGS
[0021] Exemplary embodiments of the method and apparatus for
treatment of intracranial hemorrhages are illustrated in the
accompanying drawings, which are for illustrative purposes only.
The drawings comprise the following figures, in which like numerals
indicate like parts.
[0022] FIG. 1 is a schematic illustration of an ultrasonic catheter
configured for insertion into large vessels of the human body.
[0023] FIG. 2A is a cross-sectional view of the ultrasonic catheter
of FIG. 1 taken along line 2-2.
[0024] FIG. 2B is a cross-sectional view of another embodiment of
the ultrasonic catheter of FIG. 1 taken along line 2-2.
[0025] FIG. 3 is a schematic illustration of an elongate inner core
configured to be positioned within the central lumen of the
catheter illustrated in FIGS. 2A and 2B.
[0026] FIG. 4 is a cross-sectional view of the elongate inner core
of FIG. 3 taken along line 4-4.
[0027] FIG. 5 is a schematic wiring diagram illustrating an
exemplary technique for electrically connecting five groups of
ultrasound radiating members to form an ultrasound assembly.
[0028] FIG. 6 is a schematic illustration of the ultrasound
assembly of FIG. 5 housed within the inner core of FIG. 4.
[0029] FIG. 7 is a cross-sectional view of the ultrasound assembly
of FIG. 6 taken along line 7-7.
[0030] FIG. 8 is a cross-sectional view of the ultrasound assembly
of FIG. 6 taken along line 8-8.
[0031] FIG. 9A illustrates the energy delivery section of the inner
core of FIG. 4 positioned within the energy delivery section of the
tubular body of FIG. 2A.
[0032] FIG. 9B illustrates the energy delivery section of the inner
core of FIG. 4 positioned within the energy delivery section of the
tubular body of FIG. 2B.
[0033] FIG. 10 is a cross-sectional view of the distal end of an
ultrasonic catheter having fluid delivery lumens associated with
fluid delivery ports along specific axial lengths of the ultrasonic
catheter.
[0034] FIG. 11 is a block diagram of a feedback control system for
use with an ultrasonic catheter.
[0035] FIG. 12 is a schematic illustration of an ultrasonic
catheter inserted into a treatment site through a bore in the
patient's skull.
[0036] FIG. 13 is a side view of the distal end of an ultrasonic
catheter positioned at the treatment site of FIG. 12.
[0037] FIG. 14 is a cross-sectional view of the distal end of an
ultrasonic catheter having a fluid delivery lumen and a fluid
evacuation lumen.
[0038] FIG. 15 is schematic illustration of an ultrasonic catheter
inserted into a treatment site through an external ventricular
drainage catheter.
[0039] FIGS. 16A-C are cross-sectional views along the longitudinal
axis of an embodiment of an ultrasonic catheter having an occluder
located proximal to the fluid delivery ports.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0040] As set forth above, methods and apparatuses have been
developed that allow an intracranial hemorrhage and/or a
subarachnoid hemorrhage to be treated using ultrasonic energy in
conjunction with a therapeutic compound and/or light treatment. As
used herein, the term "intracranial hemorrhage" encompasses both
intracerebral hemorrhage and intraventricular hemorrhage. Although
some embodiments may be disclosed with reference to intracerebral
hemorrhage or intraventricular hemorrhage, the embodiments can
generally be used to treat both types of intracranial hemorrhage.
Disclosed herein are several exemplary embodiments of ultrasonic
catheters that can be used to enhance the efficacy of therapeutic
compounds at a treatment site within a patient's body. Also
disclosed are exemplary methods for using such catheters. For
example, as discussed in greater detail below, the ultrasonic
catheters disclosed herein can be used to deliver a therapeutic
compound to a blood clot in the brain, allowing at least a portion
of the blood clot to be dissolved and/or removed, thereby reducing
damage to brain tissue.
[0041] As used herein, the term "therapeutic compound" refers
broadly, without limitation, and in addition to its ordinary
meaning, to a drug, medicament, dissolution compound, genetic
material or any other substance capable of effecting physiological
functions. Additionally, a mixture including substances such as
these is also encompassed within this definition of "therapeutic
compound". Examples of therapeutic compounds include thrombolytic
compounds, anti-thrombosis compounds, and other compounds used in
the treatment of vascular occlusions and/or blood clots, including
compounds intended to prevent or reduce clot formation,
neuroprotective agents, anti-apoptotic agents, and neurotoxin
scavenging agents. Exemplary therapeutic compounds include, but are
not limited to, heparin, urokinase, streptokinase, tPA, rtPA,
BB-10153 (manufactured by British Biotech, Oxford, UK), plasmin,
IIbIIa inhibitors, desmoteplase, caffeinol, deferoxamine, and
factor VIIa.
[0042] As used herein, the terms "ultrasonic energy", "ultrasound"
and "ultrasonic" refer broadly, without limitation, and in addition
to their ordinary meaning, to mechanical energy transferred through
longitudinal pressure or compression waves. Ultrasonic energy can
be emitted as continuous or pulsed waves, depending on the
parameters of a particular application. Additionally, ultrasonic
energy can be emitted in waveforms having various shapes, such as
sinusoidal waves, triangle waves, square waves, or other wave
forms. Ultrasonic energy includes sound waves. In certain
embodiments, the ultrasonic energy referred to herein has a
frequency between about 20 kHz and about 20 MHz. For example, in
one embodiment, the ultrasonic energy has a frequency between about
500 kHz and about 20 MHz. In another embodiment, the ultrasonic
energy has a frequency between about 1 MHz and about 3 MHz. In yet
another embodiment, the ultrasonic energy has a frequency of about
2 MHz. In certain embodiments described herein, the average
acoustic power of the ultrasonic energy is between about 0.01 watts
and 300 watts. In one embodiment, the average acoustic power is
about 15 watts.
[0043] As used herein, the term "ultrasound radiating member"
refers broadly, without limitation, and in addition to its ordinary
meaning, to any apparatus capable of producing ultrasonic energy.
An ultrasonic transducer, which converts electrical energy into
ultrasonic energy, is an example of an ultrasound radiating member.
An exemplary ultrasonic transducer capable of generating ultrasonic
energy from electrical energy is a piezoelectric ceramic
oscillator. Piezoelectric ceramics typically comprise a crystalline
material, such as quartz, that changes shape when an electrical
current is applied to the material. This change in shape, made
oscillatory by an oscillating driving signal, creates ultrasonic
sound waves. In other embodiments, ultrasonic energy can be
generated by an ultrasonic transducer that is remote from the
ultrasound radiating member, and the ultrasonic energy can be
transmitted, via, for example, a wire that is coupled to the
ultrasound radiating member. In such embodiments, a "transverse
wave" can be generated along the wire. As used herein is a wave
propagated along the wire in which the direction of the disturbance
at each point of the medium is perpendicular to the wave vector.
Some embodiments, such as embodiments incorporating a wire coupled
to an ultrasound radiating member for example, are capable of
generating transverse waves. See e.g., U.S. Pat. Nos. 6,866,670,
6,660,013 and 6,652,547, the entirety of which are hereby
incorporated by reference herein. Other embodiments without the
wire can also generate transverse waves along the body of the
catheter.
[0044] In certain applications, the ultrasonic energy itself
provides a therapeutic effect to the patient. Examples of such
therapeutic effects include blood clot disruption; promoting
temporary or permanent physiological changes in intracellular or
intercellular structures; and rupturing micro-balloons or
micro-bubbles for therapeutic compound delivery. Further
information about such methods can be found in U.S. Pat. Nos.
5,261,291 and 5,431,663.
[0045] FIG. 1 schematically illustrates an embodiment of an
ultrasonic catheter 10 that can be used to treat a blood clot in
the brain resulting from an intracerebral hemorrhage (ICH) and/or
an intraventricular hemorrhage (IVH).
[0046] In the illustrated embodiment, the ultrasonic catheter 10
generally includes a multi-component, elongate flexible tubular
body 12 having a proximal region 14 and a distal region 15. The
tubular body 12 includes a flexible energy delivery section 18
located in the distal region 15. The tubular body 12 and other
components of the catheter 10 can be manufactured in accordance
with a variety of techniques known to an ordinarily skilled
artisan. Suitable materials and dimensions can be readily selected
based on the natural and anatomical dimensions of the treatment
site and on the desired access site. In addition, the surface of
the catheter 10 can be coated with an antimicrobial material, such
as silver or a silver based compound.
[0047] In some embodiments, the tubular body 12 is between about
one centimeter and about six centimeters in length. In some
embodiments that are particularly suited for treating an
intraventricular hemorrhage, the tubular body 12 is between about
three centimeters and about six centimeters in length. In some
embodiments that are particularly suited for treating an
intracerebral hemorrhage, the tubular body 12 is between about one
centimeter and about three centimeters in length.
[0048] In an exemplary embodiment, the tubular body proximal region
14 comprises a material that has sufficient flexibility, hoop
strength, kink resistance, rigidity and structural support to push
the energy delivery section 18 through an opening in the skull and
then, in turn, the patient's brain tissue to a treatment site
(e.g., one of the ventricles). Examples of such materials include,
but are not limited to, extruded polytetrafluoroethylene ("PTFE"),
polyethylenes ("PE"), polyamides and other similar materials. In
certain embodiments, the tubular body proximal region 14 is
reinforced by braiding, mesh or other constructions to provide
increased kink resistance and ability to be pushed. For example,
nickel titanium or stainless steel wires can be placed along or
incorporated into the tubular body 12 to reduce kinking.
Alternatively, in some embodiments, the tubular body proximal
region can comprise a substantially rigid metal tube.
[0049] In one embodiment, the tubular body energy delivery section
18 can comprise a material that is thinner than the material
comprising the tubular body proximal region 14. In another
exemplary embodiment, the tubular body energy delivery section 18
comprises a material that has a greater acoustic transparency than
the material comprising the tubular body proximal region 14.
Thinner materials generally have greater acoustic transparency than
thicker materials. Suitable materials for the energy delivery
section 18 include, but are not limited to, high or low density
polyethylenes, urethanes, nylons, and the like. In certain modified
embodiments, the energy delivery section 18 comprises the same
material or a material of the same thickness as the proximal region
14.
[0050] In some embodiments, the distal region 15 of the catheter 10
comprises a steerable tip. The steerable tip can be constructed in
a monorail configuration in which a relatively short guidewire
lumen receives a guidewire. In the illustrated embodiment, the
catheter 10 can be constructed using an over-the-wire design in
which the guidewire is enclosed by a guidewire lumen over the
entire length of the catheter 10. In some embodiments, the catheter
10 can have a lumen that is sized and shaped to receive stylet
instead of or in addition to a guidewire. The stylet provides the
catheter with additional column strength and can be used to guide
the catheter 10 through tissue and to the blood clot, as described
in more detail below. In some embodiments, the steerable tip is
stiff enough to push through tissue and/or the blood clot, but also
is flexible enough to be bent as the catheter 10 is steered to the
blood clot. In addition, in some embodiments, the ultrasonic
catheter 10 can be inserted into the lumen of and/or attached to an
external ventricular drainage (EVD) catheter by, for example, a
clip or hook mechanism.
[0051] FIG. 2A illustrates a cross section of the tubular body 12
taken along line 2-2 in FIG. 1. In the embodiment illustrated in
FIG. 2A, three fluid delivery lumens 30a, 30b, 30c are incorporated
into the tubular body 12. In other embodiments, more or fewer fluid
delivery lumens can be incorporated into the tubular body 12. In
such embodiments, the arrangement of the fluid delivery lumens 30
provides a hollow central lumen 51 passing through the tubular body
12. The cross-section of the tubular body 12, as illustrated in
FIG. 2A, is substantially constant along the length of the catheter
10. Thus, in such embodiments, substantially the same cross-section
is present in both the proximal region 14 and the distal region 15
of the tubular body 12, including the energy delivery section
18.
[0052] In certain embodiments, the central lumen 51 has a minimum
diameter greater than about 0.030 inches. In another embodiment,
the central lumen 51 has a minimum diameter greater than about
0.037 inches. Accordingly, in one embodiment of use, the tubular
body 12 can be advanced over a guidewire (not shown) in order to
position the body 12 within the patient. In another embodiment, the
tubular body 12 is sufficiently stiff such that it can be steered
directly to the target site. In an exemplary embodiment, the fluid
delivery lumens 30 have dimensions of about 0.026 inches wide by
about 0.0075 inches high, although other dimensions can be used in
other embodiments.
[0053] In an exemplary embodiment, the central lumen 51 extends
through the length of the tubular body 12. As illustrated in FIG.
1, the central lumen 51 has a distal exit port 29 and a proximal
access port 31. The proximal access port 31 forms part of the
backend hub 33, which is attached to the tubular body proximal
region 14. In such embodiments, the backend hub also includes a
cooling fluid fitting 46, which is hydraulically connected to the
central lumen 51. In such embodiments, the backend hub 33 also
includes a therapeutic compound inlet port 32, which is
hydraulically coupled to the fluid delivery lumens 30, and which
can also be hydraulically coupled to a source of therapeutic
compound via a hub such as a Luer fitting.
[0054] FIG. 2B illustrates another embodiment of a cross section of
the tubular body 12 taken along line 2-2 in FIG. 1. In the
embodiment illustrated in FIG. 2B, six radially disposed lumens
30a-f are incorporated into the tubular body 12. Although the
lumens 30a-f are not all the same size and shape in the illustrated
embodiment, in other embodiments, the lumens 30a-f are
substantially the same size and shape. In other embodiments, one or
more lumens are sized and shaped differently than the other lumens.
In other embodiments, more or fewer radially disposed lumens can be
incorporated into the tubular body 12. In this embodiment, the
arrangement of the radially disposed lumens 30a-f also provides a
hollow central lumen 51 passing through the tubular body 12.
[0055] In some embodiments, the lumens 30a-f can be used to deliver
a fluid to a treatment site and/or to evacuate a fluid from around
a treatment site. As illustrated in FIG. 2B, the lumens 30a-f have
ports 58a-f that allow fluids to be delivered from the lumens 30a-f
and/or to be evacuated from the lumens 30a-f. These ports 58a-f can
be located axially in the distal portion of the tubular body 12 and
in or around the treatment portion of the tubular body 12. For
example, ports 58a, corresponding to lumen 30a, can be the most
proximally located ports, while ports 58b can be located just
distal of ports 58a. Ports 58c can be located just distal of ports
58b, and so on such that ports 58f are the most distally located
ports. In some embodiments, ports 58b-e are used to deliver fluids
while the outer ports 58a and 58f are used to evacuate fluids from
around the treatment site. Those of skill in the art will recognize
that the number and location of the ports used for delivering
fluids and for evacuating fluids can be modified, reduced or
increased. In one embodiment, the catheter has at least one fluid
delivery lumen and at least one evacuation lumen each with
corresponding ports.
[0056] In the illustrated embodiment, the central lumen 51 is
configured to receive an elongate inner core 34, an exemplary
embodiment of which is illustrated in FIG. 3. In such embodiments,
the elongate inner core 34 includes a proximal region 36 and a
distal region 38. A proximal hub 37 is fitted on one end of the
inner core proximal region 36. One or more ultrasound radiating
members 40 are positioned within an inner core energy delivery
section 41 that is located within the distal region 38. The
ultrasound radiating members 40 form an ultrasound assembly 42,
which will be described in greater detail below. In some
embodiments, the inner core 34 can be slid into and/or removed from
the central lumen 51 during operation. In other embodiments, the
inner core 34 can be built into the catheter 10 as a non-removable
component. In such an embodiment, the inner core 34 can include a
guidewire lumen (not shown) and/or the catheter 10 is configured to
be steerable or inserted through a guide catheter (not shown)
[0057] As shown in the cross-section illustrated in FIG. 4, which
is taken along lines 4-4 in FIG. 3, in an exemplary embodiment, the
inner core 34 has a cylindrical shape, with an outer diameter that
permits the inner core 34 to be inserted into the central lumen 51
of the tubular body 12 via the proximal access port 31. Suitable
outer diameters of the inner core 34 include, but are not limited
to, between about 0.010 inches and about 0.100 inches. In another
embodiment, the outer diameter of the inner core 34 is between
about 0.020 inches and about 0.080 inches. In yet another
embodiment, the inner core 34 has an outer diameter of about 0.035
inches.
[0058] Still referring to FIG. 4, the inner core 34 includes a
cylindrical outer body 35 that houses the ultrasound assembly 42.
The ultrasound assembly 42 includes wiring and ultrasound radiating
members, described in greater detail in FIGS. 5 through 8, such
that the ultrasound assembly 42 is capable of radiating ultrasonic
energy from the energy delivery section 41 of the inner core 34.
The ultrasound assembly 42 is electrically connected to the backend
hub 33, where the inner core 34 can be connected to a control
system 100 via cable 45 (illustrated in FIG. 1). In an exemplary
embodiment, an electrically insulating potting material 43 fills
the inner core 34, surrounding the ultrasound assembly 42, thus
reducing or preventing movement of the ultrasound assembly 42 with
respect to the outer body 35. In one embodiment, the thickness of
the outer body 35 is between about 0.0002 inches and 0.010 inches.
In another embodiment, the thickness of the outer body 35 is
between about 0.0002 inches and 0.005 inches. In yet another
embodiment, the thickness of the outer body 35 is about 0.0005
inches.
[0059] In an exemplary embodiment, the ultrasound assembly 42
includes a plurality of ultrasound radiating members 40 that are
divided into one or more groups. Each group comprises one or more
ultrasound radiating members 40. For example, FIG. 5 is a schematic
wiring diagram illustrating one technique for connecting five
groups of ultrasound radiating members 40 to form the ultrasound
assembly 42. As illustrated in FIG. 5, the ultrasound assembly 42
comprises five groups G1, G2, G3, G4, and G5 of ultrasound
radiating members 40 that are electrically connected to each other.
The five groups are also electrically connected to the control
system 100.
[0060] Still referring to FIG. 5, in an exemplary embodiment, the
control circuitry 100 includes a voltage source 102 having a
positive terminal 104 and a negative terminal 106. The negative
terminal 106 is connected to common wire 108, which connects the
five groups G1-G5 of ultrasound radiating members 40 in series. The
positive terminal 104 is connected to a plurality of lead wires
110, which each connect to one of the five groups G1-G5 of
ultrasound radiating members 40. Thus, under this configuration,
each of the five groups G1-G5 is connected to the positive terminal
104 via one of the lead wires 110, and to the negative terminal 106
via the common wire 108.
[0061] Although FIG. 5 is illustrated with five groups, the
ultrasound assembly 42 can comprise fewer or more groups. For
example, in some embodiments the ultrasound assembly 42 can
comprise about one to about nine groups. In some embodiments, each
group comprises an individually addressable ultrasound radiating
member 40. In some embodiments, each ultrasound radiating member 40
is spaced about 0.25 centimeters to about 2 centimeters apart. In
some embodiments, each ultrasound radiating member 40 is spaced
about one centimeter apart. In some embodiments, the ultrasound
radiating members 40 can be located between the fluid delivery and
fluid evacuation ports 58. This type of arrangement helps drive the
lytic drug that exits the fluid delivery port into the blood clot
instead of having the drug flow along the catheter body and into
the fluid evacuation port before acting on the blood clot.
[0062] FIG. 6 illustrates an exemplary technique for arranging the
components of the ultrasound assembly 42 (as schematically
illustrated in FIG. 5) into the inner core 34 (as schematically
illustrated in FIG. 4). FIG. 6 is a cross-sectional view of the
ultrasound assembly 42 taken within group G1 in FIG. 5, as
indicated by the presence of four lead wires 110. For example, if a
cross-sectional view of the ultrasound assembly 42 was taken within
group G4 in FIG. 5, only one lead wire 110 would be present (that
is, the one lead wire connecting group G5).
[0063] In the exemplary embodiment illustrated in FIG. 6, the
common wire 108 includes an elongate, flat piece of electrically
conductive material in electrical contact with a pair of ultrasound
radiating members 40. Each of the ultrasound radiating members 40
is also in electrical contact with a positive contact wire 112.
Because the common wire 108 is connected to the negative terminal
106, and the positive contact wire 112 is connected to the positive
terminal 104, a voltage difference can be created across each
ultrasound radiating member 40. In such embodiments, lead wires 110
are separated from the other components of the ultrasound assembly
42, thus preventing interference with the operation of the
ultrasound radiating members 40 as described above. For example, in
an exemplary embodiment, the inner core 34 is filled with an
insulating potting material 43, thus deterring unwanted electrical
contact between the various components of the ultrasound assembly
42.
[0064] FIGS. 7 and 8 illustrate cross sectional views of the inner
core 34 of FIG. 6 taken along lines 7-7 and 8-8, respectively. As
illustrated in FIG. 7, the ultrasound radiating members 40 are
mounted in pairs along the common wire 108. The ultrasound
radiating members 40 are connected by positive contact wires 112,
such that substantially the same voltage is applied to each
ultrasound radiating member 40. As illustrated in FIG. 8, the
common wire 108 includes wide regions 108W upon which the
ultrasound radiating members 40 can be mounted, thus reducing the
likelihood that the paired ultrasound radiating members 40 will
short together. In certain embodiments, outside the wide regions
108W, the common wire 108 can have a more conventional, rounded
wire shape.
[0065] The embodiments described above, and illustrated in FIGS. 5
through 8, include a plurality of ultrasound radiating members
grouped spatially. That is, in such embodiments, the ultrasound
radiating members within a certain group are positioned adjacent to
each other, such that when a single group is activated, ultrasonic
energy is delivered from a certain length of the ultrasound
assembly. However, in modified embodiments, the ultrasound
radiating members of a certain group may be spaced apart from each
other, such that the ultrasound radiating members within a certain
group are not positioned adjacent to each other. In such
embodiments, when a single group is activated, ultrasonic energy
can be delivered from a larger, spaced apart portion of the
ultrasound assembly. Such modified embodiments can be advantageous
in applications where a less focused, more diffuse ultrasonic
energy field is to be delivered to the treatment site.
[0066] In an exemplary embodiment, the ultrasound radiating members
40 comprise rectangular lead zirconate titanate ("PZT") ultrasound
transducers that have dimensions of about 0.017 inches by about
0.010 inches by about 0.080 inches. In other embodiments, other
configurations and dimensions can be used. For example, disc-shaped
ultrasound radiating members 40 or cylindrical-shaped ultrasound
radiating members 40 can be used in other embodiments. In some
embodiments, the disc-shaped or cylindrical-shaped ultrasound
radiating members 40 can have a hole or bore along the central axis
of the ultrasound radiating member 40 so that the disc-shaped
ultrasound radiating member 40 looks like a washer and the
cylindrical ultrasound radiating member 40 looks toroidal. In an
exemplary embodiment, the common wire 108 comprises copper, and is
about 0.005 inches thick, although other electrically conductive
materials and other dimensions can be used in other embodiments. In
an exemplary embodiment, lead wires 110 are 36 gauge electrical
conductors, and positive contact wires 112 are 42 gauge electrical
conductors. However, other wire gauges can be used in other
embodiments.
[0067] As described above, suitable frequencies for the ultrasound
radiating members 40 include, but are not limited to, from about 20
kHz to about 20 MHz. In one embodiment, the frequency is between
about 500 kHz and about 20 MHz, and in another embodiment the
frequency is between about 1 MHz and about 3 MHz. In yet another
embodiment, the ultrasound radiating members 40 are operated with a
frequency of about 2 MHz.
[0068] FIG. 9A illustrates the inner core 34 positioned within an
embodiment of the tubular body 12. Details of the ultrasound
assembly 42, provided in FIG. 6, are omitted for clarity. As
described above, the inner core 34 can be slid within the central
lumen 51 of the tubular body 12, thereby allowing the inner core
energy delivery section 41 to be positioned within the tubular body
energy delivery section 18. For example, in an exemplary
embodiment, the materials comprising the inner core energy delivery
section 41, the tubular body energy delivery section 18, and the
potting material 43 all comprise materials having similar acoustic
impedance, thereby minimizing ultrasonic energy losses across
material interfaces.
[0069] FIG. 9A further illustrates placement of fluid delivery
ports 58 within the tubular body energy delivery section 18. As
illustrated, holes or slits are formed from the fluid delivery
lumen 30 through the tubular body 12, thereby permitting fluid flow
from the fluid delivery lumen 30 to the treatment site. A plurality
of fluid delivery ports 58 can be positioned axially along the
tubular body 12. Thus, a source of therapeutic compound coupled to
the inlet port 32 provides a hydraulic pressure which drives the
therapeutic compound through the fluid delivery lumens 30 and out
the fluid delivery ports 58.
[0070] By spacing the fluid delivery lumens 30 around the
circumference of the tubular body 12 substantially evenly, as
illustrated in FIG. 9A, a substantially uniform flow of therapeutic
compound around the circumference of the tubular body 12 can be
achieved. Additionally, the size, location and geometry of the
fluid delivery ports 58 can be selected to provide uniform fluid
flow from the fluid delivery ports 30 to the treatment site. For
example, in one embodiment, fluid delivery ports closer to the
proximal region of the energy delivery section 18 have smaller
diameters than fluid delivery ports closer to the distal region of
the energy delivery section 18, thereby allowing uniform delivery
of therapeutic compound in the energy delivery section.
[0071] For example, in one embodiment in which the fluid delivery
ports 58 have similar sizes along the length of the tubular body
12, the fluid delivery ports 58 have a diameter between about
0.0005 inches to about 0.0050 inches. In another embodiment in
which the size of the fluid delivery ports 58 changes along the
length of the tubular body 12, the fluid delivery ports 58 have a
diameter between about 0.001 inches to about 0.005 inches in the
proximal region of the energy delivery section 18, and between
about 0.005 inches to about 0.0020 inches in the distal region of
the energy delivery section 18. The increase in size between
adjacent fluid delivery ports 58 depends on a variety of factors,
including the material comprising the tubular body 12, and on the
size of the fluid delivery lumen 30. The fluid delivery ports 58
can be created in the tubular body 12 by punching, drilling,
burning or ablating (such as with a laser), or by other suitable
methods. Therapeutic compound flow along the length of the tubular
body 12 can also be increased by increasing the density of the
fluid delivery ports 58 toward the distal region of the energy
delivery section.
[0072] In certain applications, a spatially nonuniform flow of
therapeutic compound from the fluid delivery ports 58 to the
treatment site is to be provided. In such applications, the size,
location and geometry of the fluid delivery ports 58 can be
selected to provide such nonuniform fluid flow.
[0073] In another embodiment, one or more of the fluid delivery
lumens 30 can be used to evacuate fluid and material from the
treatment site. In such an embodiment, a lumen 30 can be connected
to a vacuum source (e.g., a pump).
[0074] Referring still to FIG. 9A, placement of the inner core 34
within the tubular body 12 further defines cooling fluid lumens 44.
Cooling fluid lumens 44 are formed between an outer surface 39 of
the inner core 34 and an inner surface 16 of the tubular body 12.
In certain embodiments, a cooling fluid is introduced through the
proximal access port 31 such that cooling fluid flows through
cooling fluid lumens 44 and out of the catheter 10 through distal
exit port 29 (see FIG. 1). In other embodiments, the cooling fluid
does not flow out of the catheter 10 and is instead recirculated
within the catheter 10. In an exemplary embodiment, the cooling
fluid lumens 44 are substantially evenly spaced around the
circumference of the tubular body 12 (that is, at approximately 120
degree increments for a three-lumen configuration), thereby
providing substantially uniform cooling fluid flow over the inner
core 34. Such a configuration advantageously removes thermal energy
from the treatment site. As will be explained below, the flow rate
of the cooling fluid and the power to the ultrasound assembly 42
can be adjusted to maintain the temperature of the inner core
energy delivery section 41, or of the treatment site generally,
within a desired range. In another embodiment, a cooling rod made
of a thermally conductive material, such as a metal like copper for
example, can be used to cool the catheter by acting as a heat sink.
The cooling rod can be a thick copper wire that is incorporated
into the inner core 34 as part of the wiring for the circuitry.
Alternatively, the cooling rod can be sized, shaped and cofigured
to be inserted into a lumen in the catheter, for example the
guidewire or stylet lumen or cooling lumens. The cooling rod can be
used instead of or in conjunction with liquid cooling.
[0075] In another embodiment, the cooling fluid lumen 44 can be
used to evacuate the treatment site. In such an embodiment, the
cooling fluid lumen 44 can be connected to a vacuum source (e.g., a
pump). In this manner, clot material from the treatment site can be
removed to reduce pressure at the treatment site. In addition,
removal of some elements of the clot material that can cause tissue
damage or reduce the rate of healing, such as iron and hemoglobin
for example, can help reduce further tissue damage to the brain and
promote healing. Fluid can be simultaneously delivered to the clot,
with for example lytics and the delivery of ultrasound energy as
described herein, from a fluid delivery lumen while fluid is being
removed from a fluid removal lumen in a lavage treatment. A single
pump configured to provide two actions, fluid delivery and fluid
removal, can be used to perform the lavage. Alternatively, two
separate pumps can be used, one pump for fluid delivery and another
pump for fluid removal.
[0076] In an exemplary embodiment, the inner core 34 can be rotated
or moved within the tubular body 12. Specifically, movement of the
inner core 34 can be accomplished by maneuvering the proximal hub
37 while holding the backend hub 33 stationary. The inner core
outer body 35 is at least partially constructed from a material
that provides enough structural support to permit movement of the
inner core 34 within the tubular body 12 without kinking of the
tubular body 12. Additionally, in an exemplary embodiment, the
inner core outer body 35 comprises a material having the ability to
transmit torque. Suitable materials for the inner core outer body
35 include, but are not limited to, polyimides, polyesters,
polyurethanes, thermoplastic elastomers and braided polyimides. In
other embodiments, as mentioned above, the inner core 34 can be
coupled to the tubular body 12 or integrally formed with the
tubular body 12 to form one part.
[0077] In an exemplary embodiment, the fluid delivery lumens 30 and
the cooling fluid lumens 44 are open at the distal end of the
tubular body 12, thereby allowing the therapeutic compound and the
cooling fluid to pass into the patient's vasculature at the distal
exit port 29. In a modified embodiment, the fluid delivery lumens
30 can be selectively occluded at the distal end of the tubular
body 12, thereby providing additional hydraulic pressure to drive
the therapeutic compound out of the fluid delivery ports 58. In
either configuration, the inner core 34 can be prevented from
passing through the distal exit port 29 by providing the inner core
34 with a length that is less than the length of the tubular body
12. In other embodiments, a protrusion is formed within the tubular
body 12 in the distal region 15, thereby preventing the inner core
34 from passing through the distal exit port 29.
[0078] In other embodiments, the catheter 10 includes an occlusion
device positioned at the distal exit port 29. In such embodiments,
the occlusion device has a reduced inner diameter that can
accommodate a guidewire, but that is less than the inner diameter
of the central lumen 51. Thus, the inner core 34 is prevented from
extending past the occlusion device and out the distal exit port
29. For example, suitable inner diameters for the occlusion device
include, but are not limited to, between about 0.005 inches and
about 0.050 inches. In other embodiments, the occlusion device has
a closed end, thus preventing cooling fluid from leaving the
catheter 10, and instead recirculating to the tubular body proximal
region 14. These and other cooling fluid flow configurations permit
the power provided to the ultrasound assembly 42 to be increased in
proportion to the cooling fluid flow rate. Additionally, certain
cooling fluid flow configurations can reduce exposure of the
patient's body to cooling fluids.
[0079] In an exemplary embodiment, such as illustrated in FIG. 9A,
the tubular body 12 includes one or more temperature sensors 20
that are positioned within the energy delivery section 18. In such
embodiments, the tubular body proximal region 14 includes a
temperature sensor lead which can be incorporated into cable 45
(illustrated in FIG. 1). Suitable temperature sensors include, but
are not limited to, temperature sensing diodes, thermistors,
thermocouples, resistance temperature detectors ("RTDs") and fiber
optic temperature sensors which use thermalchromic liquid crystals.
Suitable temperature sensor 20 geometries include, but are not
limited to, a point, a patch or a stripe. The temperature sensors
20 can be positioned within one or more of the fluid delivery
lumens 30, and/or within one or more of the cooling fluid lumens
44.
[0080] FIG. 9B illustrates the inner core 34 positioned within the
embodiment of the tubular body 12 illustrated in FIG. 2B. This
embodiment is similar to and incorporates many of the features of
the embodiment described above with respect to FIG. 9A. As
illustrated in FIG. 9B, the tubular body 12 has six radially
disposed lumens 30a-f with corresponding ports 58a-f for fluid
delivery and/or fluid evacuation. Lumens used for fluid evacuation
can have multiple fluid evacuation ports to reduce the likelihood
that all ports of a particular lumen will be blocked or occluded
simultaneously. In some embodiments, each lumen used for fluid
evacuations has three (3) or more fluid evacuation ports, while in
other embodiments, each lumen has less than three (3) fluid
evacuation ports. As mentioned above, in modified embodiments, the
number and or orientation of the fluid delivery or evacuations and
the associated ports can be modified and/or changed. The inner core
34 is disposed within the central lumen 51, resulting in the
formation of three interconnected cooling fluid lumens 44 that
surround the outer surface 39 of the inner core 44. The cooling
fluid can be used to prevent the catheter from overheating and/or
to provide localized hypothermia to portions of the brain.
Alternatively, thermoelectric cooling may be used instead of
cooling fluid to prevent overheating or provide localized
hypothermia. In some embodiments, the cooling fluid is retained
within the catheter 10. Retaining cooling fluid within the catheter
10 can be particularly advantageous in applications involving the
treatment of intracerebral hemorrhages, where it is often desirable
to reduce intracranial pressure.
[0081] The inner core 34 is similar to the inner core 34 described
above in connection with FIGS. 3 and 4. Briefly, the inner core 34
includes a cylindrical outer body 35 that houses the ultrasound
assembly 42. In an exemplary embodiment, an electrically insulating
potting material 43 fills the inner core 34 and surrounds the
ultrasound assembly 42.
[0082] In some embodiments as illustrated in FIG. 9B, at least one
light source 200 can be positioned the tubular body 12. The light
source 200 can be, for example, a light emitting diode (LED) or
fiber optic based source connected to an external light source. In
some embodiments, LEDs may be mounted on the catheter 1 in the
treatment zone. For a fiber optic based source, the external light
source can be a filtered broad band light source, or alternatively,
a laser. The wavelength and amplitude of light is selected for its
ability to penetrate clot and brain tissue while enhancing
performance and survival of mitochondria exposed to free hemoglobin
and iron. Light can be delivered in a pulsed, chopped, or
continuous manner or a combination of the above, to balance any
heat generation with mitochondria stimulation and/or
protection.
[0083] As illustrated in FIG. 9B and discussed above in the
embodiment illustrated in FIG. 9A, a temperature sensor 20 located
in the energy delivery section of the catheter 10 can be used to
monitor and regulate the temperature of the device.
[0084] In some embodiments, a pressure sensor 202 is located in one
or more of the radially disposed lumens 30a-f and near a port
58a-f. For example, in some embodiments one pressure sensor 202 can
be located in a fluid delivery lumen 30a near a fluid delivery port
58a, and a second pressure sensor 202 can be located in a fluid
evacuation lumen 30f near a fluid evacuation port 58f. By
calculating the pressure drop across a port, the pressure outside
the device, i.e. the intracranial pressure around the catheter, can
be determined. In other embodiments, the pressure sensor 202 is
exposed to the fluid surrounding the outside of the catheter 10 and
can directly measure intracranial pressure around the catheter 10.
In some embodiments, the pressure sensor 202 can be located at the
distal tip of the catheter 10 or in the distal region 15 of the
catheter 10. In some embodiments, the pressure sensor 202 can be
based on strain gauge technology, fiber optic technology or a
semiconductor piezoresistive technology, for example. In some
embodiments, the ultrasound radiating member 40 can also be a
pressure sensor 202 or can incorporate a pressure sensor 202. In
some embodiments, the pressure sensor 202 is in fluid communication
with intracranial fluids via a lumen. A measurement of a drop in
intracranial pressure can indicate that the treatment is working to
reduce the size of the blood clot, thereby reducing the pressure
exerted by the blood clot on brain tissue.
[0085] Measuring the pressure within the lumens 30a-f and around
the catheter 10 can be useful for a variety of reasons. For
example, it is generally desirable to provide low negative pressure
to the evacuation lumens in order to reduce the risk of sucking
solid material, such as brain matter, into the evacuation lumen.
Furthermore, because reduction of intracranial pressure is often
desirable in treating ICH, it is often desirable to deliver fluids
with little pressure differential between the delivery pressure and
the intracranial pressure around the catheter. In addition,
monitoring the pressure can allow the detection of clogged or
obstructed ports which would inhibit fluid delivery and/or fluid
evacuation. This pressure data can be used as part of a feedback
control system for the fluid delivery and evacuation system.
[0086] FIG. 10 illustrates an embodiment in which the treatment
region is divided into treatment sub-regions. In the illustrated
exemplary embodiment, the tubular body 12 is subdivided into two
sub-regions A and B. Although the sub-regions are illustrated as
being approximately the same length in FIG. 10, they need not have
the same length in other embodiments. Furthermore, more than or
fewer than three treatment sub-regions can be used in other
embodiments.
[0087] In one embodiment as illustrated in FIG. 10, the catheter is
configured such that fluid delivery is controllable between the
sub-regions. Fluid control between the sub-regions is accomplished
by using the fluid delivery lumens 30a, 30b incorporated into the
interior of the tubular body. In such embodiments, fluid delivery
lumen 30a has fluid delivery ports 58a in region A of the tubular
body and fluid delivery lumen B has fluid delivery ports 58b in
region B of the tubular body. By passing a therapeutic compound
along a selected fluid delivery lumen A or B, this configuration
allows a therapeutic compound to be delivered along selected axial
regions of the tubular body 12.
[0088] In a modified embodiment, different therapeutic compounds
are passed through different fluid delivery lumens. For example, in
one embodiment a first therapeutic compound is delivered to one or
more end portions of a blood clot, such as a proximal end and a
distal end of the vascular blockage. Similarly, a second
therapeutic compound is delivered to an internal portion of the
blood clot. Such a configuration is particularly useful where it is
determined that the first therapeutic compound is more effective at
treating an end portion of the blood clot, and the second
therapeutic compound is more effective at treating an internal
portion of the blood clot. In another embodiment, the second (or
first) therapeutic compound may activate or react with the first
(or second) therapeutic compound to create the desired therapeutic
affect. In another embodiment, one therapeutic compound can be
delivered to provide neuroprotective effects. For example, the
neuroprotective compound can be delivered to brain tissue
surrounding the clot. Similarly, drugs that counteract cytotoxic
compounds in the blood clot can be delivered to the blood clot
and/or brain tissue surrounding the clot. In some embodiments, a
blood clotting drug can be delivered if bleeding in the brain is
detected.
[0089] In another modified embodiment, the catheter is configured
with more than or fewer than two treatment sub-regions. In such
embodiments, the catheter optionally includes more than or fewer
than two fluid delivery lumens with the fluid delivery ports of
each lumen being associated with a specific sub-region. For
example, in one such embodiment, a catheter includes three fluid
delivery lumens, each configured to deliver a therapeutic compound
to one of three treatment regions.
[0090] In yet another modified embodiment, one or more of the fluid
delivery lumens is configured to have fluid delivery ports in more
than one treatment sub-region. For example, in one such embodiment,
a catheter with three delivery lumens and four treatment regions
includes a delivery lumen that is configured to deliver therapeutic
compound to more than one treatment region.
[0091] In yet another modified embodiment, the number of
sub-regions along the tubular body is greater than or less than the
number of fluid delivery lumens incorporated into the tubular body.
For example, in one such embodiment, a catheter has two treatment
regions and three delivery lumens. This configuration provides one
dedicated delivery lumen for each of the treatment regions, as well
as providing a delivery lumen capable of delivering a therapeutic
compound to both treatment regions simultaneously.
[0092] In the embodiments disclosed herein, the delivery lumens
optionally extend to the distal end of the catheter. For example,
in one embodiment, a delivery lumen that is configured to deliver a
therapeutic compound to a proximal end of the blood clot does not
extend to the distal end of the catheter.
[0093] In one embodiment, a tubular body has a treatment region of
length 3n cm that is divided into three regions, each of length n
cm. The tubular body has three fluid delivery lumens incorporated
therein. A first fluid delivery lumen contains fluid delivery ports
along the first region for a total of n cm of fluid delivery ports.
A second fluid delivery lumen contains fluid delivery ports along
the first and second regions for a total of 2n cm of fluid delivery
ports. A third fluid delivery lumen contains fluid delivery ports
along all 3n cm of the tubular body treatment region. Therapeutic
compound can be delivered through one, two, or all three of the
fluid delivery lumens depending on the length of the blood clot to
be treated. In one such embodiment, n=1. In other embodiments n has
a value between about zero and about two.
[0094] The dimensions of the treatment regions and the fluid
delivery lumens provided herein are approximate. Other lengths for
fluid delivery lumens and treatment regions can be used in other
embodiments.
[0095] The ultrasound assembly has a length that may be shorter
than, longer than, or equal to a length of one the treatment
regions A and B in the tubular body 12. For example, in one
embodiment the length of the ultrasound assembly is an integral
multiple of length of an ultrasound radiating member group, as
illustrated in FIG. 5. In one embodiment, the length of an
ultrasound radiating member group is approximately 3 cm, and the
length of a treatment region A and B in the tubular body is also
about 3 cm. In another embodiment, the length of the tubular body
treatment regions is an integral multiple of the length of an
ultrasound radiating member group. For example, in one such
embodiment the ultrasound radiating member groups are 1 cm long,
and the tubular body treatment regions A and B are 2 cm long. In
such embodiments, there is optionally more than one ultrasound
radiating member group associated with each tubular body treatment
region A and B.
[0096] An ultrasonic catheter with fluid delivery sub-regions is
particularly advantageous in embodiments wherein the blood clot to
be treated is elongated. For example, in one application, a
therapeutic compound is delivered to a selected sub-region of the
blood clot. Thus, if treatment progresses faster in a particular
sub-region of the blood clot, the therapeutic compound and
ultrasonic energy delivered to that region of the occlusion can be
selectively reduced or terminated, and the treatment can move to
other regions of the blood clot.
[0097] An ultrasonic catheter with fluid delivery sub-regions can
be used to treat blood clots having a wide variety of different
lengths. For example, to treat a relatively short blood clot, a
distal portion of the tubular body is delivered to the treatment
site, and therapeutic compound is passed through a fluid delivery
lumen having fluid delivery sub-regions in the distal portion of
the tubular body. This same catheter can also be used to treat a
relatively long blood clot by using more of the flow regions. In
this manner, a single tubular body can be used to treat different
lengths of blood clots, thereby reducing inventory costs.
[0098] Additionally, in some embodiments the ultrasound radiating
member groups of the ultrasonic assembly are configured to
correspond to the fluid delivery sub-regions. In this manner,
ultrasonic energy is selectively applied to the sub-regions that
are positioned in or adjacent to the blood clot. Furthermore, such
an arrangement ensures that drugs delivered via the fluid delivery
ports will be within the effect of the ultrasonic field generated
by the ultrasonic assembly. Thus, in such embodiments, a single
ultrasonic assembly and a single drug delivery catheter are used to
treat blood clots of different lengths.
[0099] In one embodiment, the number and lengths of the treatment
regions A and B is chosen based upon the observed or calculated
distribution of blood clot lengths in the patient population. That
is, number and lengths of the sub-region are chosen to correspond
to common blood clot lengths in many patients. In a similar manner,
the number and lengths of the ultrasound radiating members is also
optionally configured to correspond to common blood clot
lengths.
[0100] In some of the embodiments described above, by controlling
flow into the treatment sub-regions, non-uniform flow is delivered
to the treatment site in the patient's vasculature. In some
embodiments, the amount of flow delivered to each treatment
sub-region is configured so as to produce improved treatment
results for a given occlusion length. Additionally, the flow within
each treatment sub-region is optionally manipulated by configuring
the size, location and/or geometry of the fluid delivery ports to
achieve uniform or non-uniform flow delivery within the treatment
sub-region. Such techniques are optionally combined with selective
electronic control of the ultrasound radiating member groups within
treatment sub-regions. For example, the ultrasound radiating
members can be repeatedly activated in a sequential order in an
axial direction to create an acoustic peristaltic pump effect that
drives fluid delivered from the fluid delivery ports in both a
radial and axial direction.
[0101] FIG. 11 schematically illustrates one embodiment of a
feedback control system 68 that can be used with the catheter 10.
The feedback control system 68 can be integrated into the control
system 100 that is connected to the inner core 34 via cable 45 (as
illustrated in FIG. 1). The feedback control system 68 allows the
temperature at each temperature sensor 20 to be monitored and
allows the output power of the energy source 70 to be adjusted
accordingly. In some embodiments, each ultrasound radiating member
40 is associated with a temperature sensor 20 that monitors the
temperature of the ultrasound radiating member 40 and allows the
feedback control system 68 to control the power delivered to each
ultrasound radiating member 40. In some embodiments, the ultrasound
radiating member 40 itself is also a temperature sensor 20 and can
provide temperature feedback to the feedback control system 68. In
addition, the feedback control system 68 allows the pressure at
each pressure sensor 202 to be monitored and allows the output
power of the energy source 70 to be adjusted accordingly. A
physician can, if desired, override the closed or open loop
system.
[0102] In an exemplary embodiment, the feedback control system 68
includes an energy source 70, power circuits 72 and a power
calculation device 74 that is coupled to the ultrasound radiating
members 40 and a pump 204. A temperature measurement device 76 is
coupled to the temperature sensors 20 in the tubular body 12. A
pressure measurement device 206 is coupled to the pressure sensors
202. A processing unit 78 is coupled to the power calculation
device 74, the power circuits 72 and a user interface and display
80.
[0103] In an exemplary method of operation, the temperature at each
temperature sensor 20 is determined by the temperature measurement
device 76. The processing unit 78 receives each determined
temperature from the temperature measurement device 76. The
determined temperature can then be displayed to the user at the
user interface and display 80.
[0104] In an exemplary embodiment, the processing unit 78 includes
logic for generating a temperature control signal. The temperature
control signal is proportional to the difference between the
measured temperature and a desired temperature. The desired
temperature can be determined by the user (as set at the user
interface and display 80) or can be preset within the processing
unit 78.
[0105] In such embodiments, the temperature control signal is
received by the power circuits 72. The power circuits 72 are
configured to adjust the power level, voltage, phase and/or current
of the electrical energy supplied to the ultrasound radiating
members 40 from the energy source 70. For example, when the
temperature control signal is above a particular level, the power
supplied to a particular group of ultrasound radiating members 40
is reduced in response to that temperature control signal.
Similarly, when the temperature control signal is below a
particular level, the power supplied to a particular group of
ultrasound radiating members 40 is increased in response to that
temperature control signal. After each power adjustment, the
processing unit 78 monitors the temperature sensors 20 and produces
another temperature control signal which is received by the power
circuits 72.
[0106] In an exemplary method of operation, the pressure at each
pressure sensor 202 is determined by the pressure measurement
device 206. The processing unit 78 receives each determined
pressure from the pressure measurement device 206. The determined
pressure can then be displayed to the user at the user interface
and display 80.
[0107] In an exemplary embodiment, the processing unit 78 includes
logic for generating a pressure control signal. The pressure
control signal is proportional to the difference between the
measured pressure and a desired pressure. The desired pressure can
be determined by the user (as set at the user interface and display
80) or can be preset within the processing unit 78.
[0108] As noted above, it is generally desirable to provide low
negative pressure to the evacuation lumens in order to reduce the
risk of sucking solid material, such as brain matter, into the
evacuation lumen. Furthermore, because reduction of intracranial
pressure is often desirable in treating ICH, it is often desirable
to deliver fluids with little pressure differential between the
delivery pressure and the intracranial pressure around the
catheter. Accordingly, the processing unit 78 can be configured to
monitor the pressure and modify or cease the delivery of fluid
and/or increase evacuation of fluid to the treatment site if
intracranial pressure increases beyond a specified limit.
[0109] In other embodiments, the pressure control signal is
received by the power circuits 72. The power circuits 72 are
configured to adjust the power level, voltage, phase and/or current
of the electrical energy supplied to the pump 204 from the energy
source 70. For example, when the pressure control signal is above a
particular level, the power supplied to a particular pump 204 is
reduced in response to that pressure control signal. Similarly,
when the pressure control signal is below a particular level, the
power supplied to a particular pump 204 is increased in response to
that pressure control signal. After each power adjustment, the
processing unit 78 monitors the pressure sensors 202 and produces
another pressure control signal which is received by the power
circuits 72.
[0110] In an exemplary embodiment, the processing unit 78
optionally includes safety control logic. The safety control logic
detects when the temperature at a temperature sensor 20 and/or the
pressure at a pressure sensor 202 exceeds a safety threshold. In
this case, the processing unit 78 can be configured to provide a
temperature control signal and/or pressure control signal which
causes the power circuits 72 to stop the delivery of energy from
the energy source 70 to that particular group of ultrasound
radiating members 40 and/or that particular pump 204.
[0111] Because, in certain embodiments, the ultrasound radiating
members 40 are mobile relative to the temperature sensors 20, it
can be unclear which group of ultrasound radiating members 40
should have a power, voltage, phase and/or current level
adjustment. Consequently, each group of ultrasound radiating
members 40 can be identically adjusted in certain embodiments. For
example, in a modified embodiment, the power, voltage, phase,
and/or current supplied to each group of ultrasound radiating
members 40 is adjusted in response to the temperature sensor 20
which indicates the highest temperature. Making voltage, phase
and/or current adjustments in response to the temperature sensed by
the temperature sensor 20 indicating the highest temperature can
reduce overheating of the treatment site.
[0112] The processing unit 78 can also be configured to receive a
power signal from the power calculation device 74. The power signal
can be used to determine the power being received by each group of
ultrasound radiating members 40 and/or pump 204. The determined
power can then be displayed to the user on the user interface and
display 80.
[0113] As described above, the feedback control system 68 can be
configured to maintain tissue adjacent to the energy delivery
section 18 below a desired temperature. For example, in certain
applications, tissue at the treatment site is to have a temperature
increase of less than or equal to approximately 6 degrees C. As
described above, the ultrasound radiating members 40 can be
electrically connected such that each group of ultrasound radiating
members 40 generates an independent output. In certain embodiments,
the output from the power circuit maintains a selected energy for
each group of ultrasound radiating members 40 for a selected length
of time.
[0114] The processing unit 78 can comprise a digital or analog
controller, such as a computer with software. In embodiments
wherein the processing unit 78 is a computer, the computer can
include a central processing unit ("CPU") coupled through a system
bus. In such embodiments, the user interface and display 80 can
include a mouse, a keyboard, a disk drive, a display monitor, a
nonvolatile memory system, and/or other computer components. In an
exemplary embodiment, program memory and/or data memory is also
coupled to the bus.
[0115] In another embodiment, in lieu of the series of power
adjustments described above, a profile of the power to be delivered
to each group of ultrasound radiating members 40 can be
incorporated into the processing unit 78, such that a preset amount
of ultrasonic energy to be delivered is pre-profiled. In such
embodiments, the power delivered to each group of ultrasound
radiating members 40 is provided according to the preset
profiles.
[0116] In an exemplary embodiment, the ultrasound radiating members
are operated in a pulsed mode. For example, in one embodiment, the
time average power supplied to the ultrasound radiating members is
between about 0.1 watts and about 2 watts. In another embodiment,
the time average power supplied to the ultrasound radiating members
is between about 0.5 watts and about 1.5 watts. In yet another
embodiment, the time average power supplied to the ultrasound
radiating members is approximately 0.6 watts or approximately 1.2
watts. In an exemplary embodiment, the duty cycle is between about
1% and about 50%. In another embodiment, the duty cycle is between
about 5% and about 25%. In yet another embodiment, the duty cycles
is approximately 7.5% or approximately 15%. In an exemplary
embodiment, the pulse averaged power is between about 0.1 watts and
about 20 watts. In another embodiment, the pulse averaged power is
between approximately 5 watts and approximately 20 watts. In yet
another embodiment, the pulse averaged power is approximately 8
watts or approximately 16 watts. The amplitude during each pulse
can be constant or varied.
[0117] In an exemplary embodiment, the pulse repetition rate is
between about 5 Hz and about 150 Hz. In another embodiment, the
pulse repetition rate is between about 10 Hz and about 50 Hz. In
yet another embodiment, the pulse repetition rate is approximately
30 Hz. In an exemplary embodiment, the pulse duration is between
about 1 millisecond and about 50 milliseconds. In another
embodiment, the pulse duration is between about 1 millisecond and
about 25 milliseconds. In yet another embodiment, the pulse
duration is approximately 2.5 milliseconds or approximately 5
milliseconds.
[0118] For example, in one particular embodiment, the ultrasound
radiating members are operated at an average power of approximately
0.6 watts, a duty cycle of approximately 7.5%, a pulse repetition
rate of approximately 30 Hz, a pulse average electrical power of
approximately 8 watts and a pulse duration of approximately 2.5
milliseconds.
[0119] In an exemplary embodiment, the ultrasound radiating member
used with the electrical parameters described herein has an
acoustic efficiency greater than approximately 50%. In another
embodiment, the ultrasound radiating member used with the
electrical parameters described herein has an acoustic efficiency
greater than approximately 75%. As described herein, the ultrasound
radiating members can be formed in a variety of shapes, such as,
cylindrical (solid or hollow), flat, bar, triangular, and the like.
In an exemplary embodiment, the length of the ultrasound radiating
member is between about 0.1 cm and about 0.5 cm, and the thickness
or diameter of the ultrasound radiating member is between about
0.02 cm and about 0.2 cm.
[0120] FIG. 12 illustrates an ultrasonic catheter 10 inserted into
a blood clot 300 through a bore 302 in the patient's skull 304.
Before insertion of the catheter 10, the bore 10 is made by making
a very small burr-hole or drill hole in the patient's skull just
large enough to permit insertion of the catheter 10. In some
embodiments, the burr-hole is larger than a drill hole. In some
embodiments, the burr-hole can be located for an occipital approach
if the patient has an intraventricular hemorrhage. In some
embodiments, the burr-hole can be located for a more frontal
approach if the patient has an intracerebral hemorrhage located in
the frontal portion of the brain. It should be appreciated that the
location of the burr-hole or drill hole can be selected to reduce
the path length between the blood clot and the hole in the
patient's skull. In addition, it may be desirable in some cases to
approach the blood clot from an angle that avoids certain portions
of the brain. Next, the dura is dissected by a rigid obturator or
by a scalpel. As shown in FIG. 13, the tubular body 12 of the
catheter 10 is then mounted over the obturator 310, and the
assembly is slid into position within the blood clot 300 with
fluoroscopic, magnetic resonance, neuronavigation, and/or computed
tomography visualization. The obturator 310 can both plug the end
of the catheter 10 and provide the catheter 10 with additional
stiffness during insertion into the brain.
[0121] After the catheter 10 is in position, a slidable sealing
surface 306 on the proximal portion of the catheter 10 can be slid
down along the catheter 10 shaft to anchor on the dermis of the
patient's head. The slidable sealing surface 306 can have sewing
holes and/or an adhesive to form a secure and relatively
water-tight seal around the bore and catheter 10. The slidable
sealing surface can be formed, for example, from a disk made of two
layers. The first layer can have a slit that permits passage of an
instrument but is otherwise generally closed. The second layer can
be made of an elastic material and have a hole with a diameter
slightly less than the diameter of the catheter 10 shaft, so that
insertion of the catheter 10 shaft through the hole results in a
tight seal.
[0122] The obturator 310 can then be removed and replaced with the
inner core 34. Drug infusion is then initiated via a constant
infusion pump along with a constant evacuation of fluid at a low
negative pressure and at a rate equal or approximately equal to the
rate of fluid delivery from the drug infusion. As the blood clot
300 is liquefied, it may be desirable in some embodiments to
increase the evacuation of fluid to reduce the intracranial
pressure. In this situation, the rate of evacuation may be greater
than the rate of fluid delivery. Ultrasound is also initiated
during drug infusion, so that the thrombolytic drug acts more
efficiently on the blood clot 300. Light sources can also be
activated after the catheter 10 has been inserted into the blood
clot 300.
[0123] Examples of thrombolytic drugs include rt-PA and t-PA. In
some embodiments, approximately 2,000 IU/mL to 50,000 IU/mL of
rt-PA is delivered at a flow rate of approximately 1 mL/hr to 25
mL/hr. In other embodiments, approximately 10,000 IU/mL of rt-PA is
delivered at a flow rate of approximately 5 mL/hr.
[0124] Because the ICH blood clot 300 is generally displacing brain
tissue, as lysis of the blood clot 300 proceeds and liquefied blood
clot 300 material is evacuated, the remaining portions of the blood
clot 300 will tend to move towards the treatment portion of the
catheter. This phenomenon enhances the blood clot 300 lysis
process, making it more efficient.
[0125] FIG. 14 illustrates one embodiment of an ultrasonic catheter
400 that is suitable for treating an ICH or IVH. The catheter 400
comprises an elongate tubular body 402 with a central lumen 404, a
fluid delivery lumen 406 and a fluid evacuation lumen 408, which
can be arranged as described above. The central lumen 404 receives
an inner core 410 comprising a plurality of ultrasound radiating
member 412. A drug, such as a thrombolytic drug, can be delivered
from the fluid delivery lumen via fluid delivery ports 414. Fluids
surround the catheter 400, such as blood, portions of a dissolved
blood clot and/or cerebral spinal fluid can be evacuated into the
fluid evacuation lumen 408 via fluid evacuation ports 416. In some
embodiments, the fluid evacuation ports 416 are relatively large,
and can have a diameter between about 0.005 to about 0.040 inches.
In other embodiments, the fluid evacuation ports 416 have a
diameter between about 0.01 to about 0.02 inches. In other
embodiments, the fluid evacuation ports 416 have a diameter of
about 0.01, 0.015 or 0.02 inches. A screen or mesh or filter can be
placed over the fluid evacuation ports 416 to reduce the likelihood
that brain tissue will be sucked into the fluid evacuation ports
416. In some embodiments, a screen or mesh can be used with an even
larger opening for fluid removal. In some embodiments, the catheter
400 can include radiopaque markers in the tubular body 402, and in
particular in the distal portion of the tubular body 402, so that
the physician can guide the insertion of the catheter 400 to the
blood clot using imaging technology, thereby minimizing or reducing
brain tissue trauma.
[0126] As described above, in some embodiments, the fluid delivery
ports 414 are spatially separated from the fluid evacuation ports
416. The fluid delivery ports 414 can be axially and/or radially
separated from the fluid evacuation ports 416. In some embodiments,
the ultrasound radiating members 412 are located axially between
the fluid delivery ports 414 and the fluid evacuation ports 416.
Such a configuration would reduce the amount of drug delivered from
the fluid delivery ports 414 from being directly evacuated by the
fluid evacuation port 416 before the delivered drug can
sufficiently act on the blood clot. In other embodiments, the fluid
delivery ports 414 are located around the ultrasound radiating
members 412 while the fluid evacuation ports 416 are located
distally or proximally of the fluid delivery ports 414. Such a
configuration allows the ultrasound energy to act upon and/or with
the drug delivered from the fluid delivery ports 414 on the blood
clot. This configuration tends to push the drug radially away from
the catheter 400 and the fluid delivery ports 414.
[0127] In some embodiments, it is desirable to maintain or reduce
intracranial pressure below a threshold or target pressure while
delivering a thrombolytic drug to the blood clot. As described
above, in some embodiments, intracranial pressure can be monitored
using a pressure sensor 420 located near the fluid evacuation port
416, or alternatively, near the fluid delivery port 414. In some
embodiments, intracranial pressure is controlled by delivery of
fluid under a positive pressure in the fluid delivery lumen 406
with respect to intracranial pressure, while maintaining a negative
pressure in the fluid evacuation lumen 408. The pressures can be
adjusted so that fluid is removed at a rate that is equal or
greater than the rate fluid is being delivered. If intracranial
pressure should be reduced, the negative pressure in the fluid
evacuation lumen 408 can be increased so that more fluid is
removed, or alternatively, the pressure in the fluid delivery lumen
406 can be reduced so that less fluid is delivered.
[0128] In some embodiments, fluid and drug delivery can be
accomplished separately and/or intermittently from fluid evacuation
to allow the drug an adequate dwell time to act on the clot before
evacuation. For example, fluid can be first evacuated from around
the blood clot, then drug can be delivered to the blood clot and
allowed to act on the blood clot for a predetermined amount of
time, and then the cycle of fluid evacuation and drug delivery can
be repeated.
[0129] Because the blood clot may be under compression by brain
tissue surrounding the clot, by continuously or periodically
draining fluid from the blood clot, the remaining unlysed portions
of the clot tends to be pushed towards the catheter 400, thereby
enhancing ultrasound and drug mediated clot lysis. In addition,
removal of the lysed portions of the clot removes toxic blood
components that can be harmful to brain tissue.
[0130] As illustrated in FIG. 15, in some embodiments, the
ultrasound catheter 400 can be used with an external ventricular
drain or drainage catheter (EVD) 422 which can be inserted to the
blood clot 424 via the burr-hole or drill hole 426 that is formed
in the patient's skull as described above. In some embodiments,
before the EVD 422 is inserted into the brain, an introducer sheath
is inserted through the burr-hole 426 and through brain tissue
until it reaches the blood clot 424, which can be located in the
ventricles 428 of the brain. In some embodiments, the introducer
sheath is about one centimeter to about nine centimeters in length.
In other embodiments, the introducer sheath is about five
centimeters to about eight centimeters in length. Once the
introducer sheath is inserted to the blood clot, the EVD can be
inserted into the introducer sheath and guided to the blood clot.
In some embodiments, the introducer sheath can then be removed.
[0131] The EVD 422 can comprise a lumen for both draining fluid
from the blood clot and for receiving the ultrasound catheter 400.
The catheter 400 can be inserted into the EVD 422 to the blood clot
424, where the ultrasound catheter 400 can deliver ultrasound
energy and/or drugs to enhance clot lysis. In some embodiments, the
ultrasound catheter 400 can be inserted alongside the EVD 422. In
some embodiments, the EVD 422 can comprise an external groove to
accommodate the ultrasound catheter 400. In some embodiments, the
ultrasound catheter 400 can be inserted into the blood clot 424
such that the ultrasound radiating members 412 in the catheter 400
extend past the distal tip of the EVD 422 and into the blood clot
424. In other embodiments, the distal portion of the EVD 422 can be
made to be ultrasound transparent so that ultrasound energy can be
transmitted through the walls of the EVD 422 to the blood clot. In
embodiments where the EVD 422 is ultrasound transparent, the
ultrasound radiating members 412 of the ultrasound catheter 400 can
remain within or alongside the EVD 422.
[0132] In some embodiments, ultrasound radiating members 412 can be
incorporated into the EVD 422. For example, the ultrasound
radiating members 412 can be formed into a cylindrical shape and
integrated into the EVD 422 such that the outer surface of the
ultrasound radiating members 412 are externally exposed on the EVD
422, thereby enhancing ultrasound radiation from the EVD 422. In
other embodiments, ultrasound radiating members 412, such as
sandwich type ultrasound radiating members 412, can be incorporated
into one lumen of a multi-lumen, ultrasound transparent EVD 422,
where the other lumens of the EVD 422 are used for drainage and/or
drug delivery. In some embodiments, drugs can be delivered to the
blood clot via the ultrasound catheter 400, a separate drug
delivery catheter or the EVD 422 itself. Where the catheter 400 is
used in conjunction with the EVD 422, the catheter 400 can
optionally include the fluid evacuation lumen 408 since fluid can
alternatively be evacuated via the EVD 422. In other embodiments,
fluid can be evacuated by both the EVD 422 and ultrasound catheter
400.
[0133] In some embodiments, an introducer sheath is not used or is
optionally used to access the blood clot. In these embodiments, a
stylet can be used to provide the ultrasound catheter 400 and/or
the EVD 422 with enough column strength to push through the brain
tissue and access the blood clot within the brain. For example, the
inner core 410 of the ultrasound catheter 400 can be removed and
the stylet can be inserted into the central lumen 404 during
insertion of the ultrasound catheter 400 into the patient's brain.
Similarly, the stylet can be inserted into the lumen of the EVD 422
during insertion of the EVD 422 into the patient's brain. After the
ultrasound catheter 400 and/or EVD 422 has been inserted, the
stylet can be removed to reduce damage to brain tissue.
[0134] In other embodiments, a flexible and/or floppy tip guidewire
is used to initially access the blood clot within the patient's
brain. The ultrasound catheter 400 and/or EVD 422 can then be
introduced over the guidewire and threaded to the blood clot. After
the ultrasound catheter 400 and/or EVD 422 has been inserted to the
blood clot, the guidewire can be removed. In other embodiments, the
guidewire can be left in place with the flexible and/or floppy tip
extending beyond the distal end of the ultrasound catheter 400 or
EVD 422 so that the flexible and/or floppy tip provides a
relatively atraumatic structure to reduce further tissue
damage.
[0135] In other embodiments, the ultrasound catheter 400 can be
delivered to the blood clot in the patient's brain through the
vasculature. A portion of a blood vessel large enough to
accommodate the ultrasound catheter 400 and near the blood clot can
be selected as a delivery zone. The blood vessel can be sealed
proximally and distally around the delivery zone using, for
example, an adhesive or an occlusion device such as an inflatable
balloon. After the vessel has been sealed, the vessel can be
perforated and the ultrasound catheter 400 can be passed through
the perforation and into the blood clot, where ultrasound energy
and drugs can be delivered to the clot while fluid is evacuated.
Alternatively, instead of perforating the vessel, the ultrasound
catheter 400 can remain within the vessel and radiate ultrasound
energy through the vessel wall and to the blood clot. Because the
vessel is not perforated, the vessel does not need to be sealed
around the delivery zone. Also, in this embodiment, drug can be
delivered to the blood clot and fluid can be evacuated from the
blood clot by a needle, an EVD 422 or other catheter.
[0136] Ultrasound energy can be delivered for a duration sufficient
to enable adequate drug distribution in and/or around the blood
clot. This can be accomplished by either intermittent or continuous
delivery of ultrasound energy. For example, ultrasound energy can
be delivered for a set time period to adequately distribute the
drug to the blood clot, and then turned off to allow the drug to
act on the blood clot. Alternatively, ultrasound energy can be
delivered substantially continuously after the drug has been
delivered to the blood clot to continuously redistribute the drug
into the blood clot as the blood clot is successfully lysed. In
addition, ultrasound energy can be delivered intermittently to
reduce heating. Also, as described in U.S. application Ser. No.
11/971,172, filed Jan. 8, 2008, which is hereby incorporated by
reference herein in its entirety, the power parameters controlling
the delivery of ultrasound energy can be randomized or varied
according to complex non-linear algorithms in order to enhance the
efficacy of the ultrasound treatment.
[0137] Drug delivery can be controlled by monitoring, for example,
lysis byproducts such as D-dimer in the effluent evacuated from the
blood clot. A high and/or increasing concentration of D-dimer in
the effluent can indicate that lysis of the blood clot is
proceeding adequately, and therefore drug delivery can be
maintained, reduced or stopped. A low or decreasing concentration
of D-dimer in the effluent can indicate that lysis of the blood
clot is inadequate or slowing or that the clot is nearly dissolved,
and therefore drug delivery can be increased if the clot is not
nearly dissolved, and reduced or stopped if lysis is almost
complete. Alternatively, lytic concentration can be monitored to
determine whether more drug should be delivered and whether lysis
is complete. In some embodiments, as lysis of the blood clot
proceeds, lytic is freed from the lysed clot, thereby increasing
the concentration of lytic in the effluent. Therefore, increased
lytic concentration can correlate to lysis completion. One way of
determining the concentration of lytic and/or D-dimer in the
effluent is to measure the color of the effluent that is evacuated
from the blood clot. The redder the effluent, the greater the
concentration of lytic and/or D-dimer in the effluent.
[0138] In some embodiments, endoscopic delivery of the ultrasound
catheter 400 to the blood clot can be used to correctly place the
ultrasound radiating members into the blood clot in the absence of
fluoroscopy.
[0139] In some embodiments, a laser can be used to ablate or
disrupt the clot, and the resulting effluent can be drained away.
In this embodiment, the wavelength of the laser is selected so that
absorption by neuronal or glial tissues is reduced, thereby
reducing tissue damage. In addition, the laser beam should avoid
being focused on blood circulating in vessels within the brain and
supplying the neuronal or glial tissues with nutrients, since the
blood can be heated by the laser and cause tissue damage.
[0140] In some embodiments, ultrasound can be transmitted from an
ultrasound radiating member located outside the patient to the
blood clot within the patient's brain through an elongate
ultrasound transmission member, which can be a vibrating wire, for
example. The proximal end of the vibrating wire can be attached to
or in communication with the ultrasound radiating member while the
distal end of the vibrating wire can be configured to deliver
ultrasound energy to the blood clot. The vibrating wire can be
inserted into the brain and to the clot through a catheter, an EVD
or other access device. Drug delivery and fluid evacuation can be
accomplished with the catheter, the EVD or the other access
device.
[0141] In some embodiments, the ultrasound catheter 400 can be used
to deliver oncological drugs, especially sonodynamic drugs, to
tumors and gliomas in the brain. The methods and apparatus
described above can be used to treat tumors and gliomas instead of
blood clots.
[0142] In some embodiments, the methods and apparatus described
above can be used to treat a blood clot in a fistula.
[0143] In some embodiments, neuroprotective drugs or agents that
assist in the functional recovery and/or the reduction of cell and
tissue damage in the brain can also be delivered to the brain and
blood clot with the methods and apparatus described above. These
neuroprotective drugs or agents can be delivered before, with, or
after the delivery of the thrombolytic drugs. Delivery of these
drugs using the methods and apparatus described above is
particularly useful where the drug delivery through the blood brain
barrier is enhanced with ultrasound treatment, or where ultrasound
enhances cell penetration by the drug, or where the drug is
sonodynamic.
[0144] In some embodiments, the ultrasound radiating member is not
inserted into the brain. Instead, after the bore hole is made and
the dura is optionally removed to expose the brain, an ultrasound
radiating member can be placed within the bore hole and on the
surface of the brain or dura to radiate ultrasound energy through
the brain and to the blood clot. In some embodiments, the
ultrasound radiating member can be disk shaped that closely matches
the size of the bore hole in the patient's skull. The disk shaped
ultrasound radiating member can be a relatively large air-backed
flat cylinder with external cooling. The large size enables the
ultrasound radiating member to operate at a relatively low
frequency. In some embodiments, a plurality of ultrasound radiating
members can be used to form a focused array to increase the
accuracy and safety of the ultrasound targeting. In some
embodiments, the disk shaped ultrasound radiating member can have a
port or hole to allow the passage of a drug deliver and/or drainage
catheter through the ultrasound radiating member.
[0145] After the ultrasound catheter 400 is inserted into the brain
and to the blood clot, a passage in the brain to the blood clot is
created. Liquid can travel up this passage and along the exterior
of the ultrasound catheter 400. In addition, the formation of the
passage in the brain tissue can cause capillary bleeding. As lytic
drug is delivered from the catheter 400 through the fluid delivery
ports 414, some of the lytic can move proximally in the passage
over the elongate tubular body 402 of the catheter 400 and inhibit
the clotting of the bleeding capillaries, thereby furthering the
bleeding into the brain. Accordingly, in some embodiments, as
illustrated in FIGS. 16A-C, the ultrasound catheter 400 further
comprises an occluder 430 located on the elongate tubular body 402
proximally of the fluid delivery ports 414. The occluder 430 can be
a low pressure balloon wrapped around the elongate tubular body 402
as shown in FIG. 16A. The low pressure balloon is designed to be
inflated at low pressures until the passage in the brain is
occluded by the balloon, thereby reducing the flow of fluids, and
lytic drug in particular, proximally of the occluder 430. The
balloon is inflated at low pressure to reduce the force exerted
against brain tissue, thereby reducing the damage to brain tissue.
In some embodiments, the balloon can be elongate, toroidal or
cuff-like.
[0146] In some embodiments, the occluder 430 can be a collar or
cuff around elongate tubular body 402 as illustrated in FIG. 16B.
The collar of cuff provides the same or similar functions as the
elongate low pressure balloon described above by occluding the
passage in the brain. The collar or cuff can be made of a elastic,
resilient and deformable material that reversibly conforms to the
shape of the passage while exerting low levels of force against the
brain tissue. The force exerted by the collar or cuff against the
brain tissue is sufficient to form an adequate seal while
minimizing and/or reducing the damage to brain tissue.
[0147] In some embodiments, the occluder 430 can be a flap or
series of flaps attached to the elongate tubular body 402 as shown
in FIG. 16C. The flaps can be oriented either towards the proximal
end or the distal end of the ultrasound catheter 400. The flaps
have the same or similar function as the elongate low pressure
balloon described above. The flaps can be designed to extend
axially at a shallow angle. In some embodiments, the flap can be
generally frustoconical in shape. In some embodiments, one end of
the flap is attached to the elongate tubular body 402 while the
free end is inwardly curved to provide an atraumatic surface. In
some embodiments, both ends of the flaps are attached to the
elongate tubular body 402 to form a collar or cuff-like structure.
The flap or flaps can be flexible, elastic and resilient so that
the flaps can press against the brain tissue and form a seal while
minimizing and/or reducing the damage to brain tissue.
[0148] While the foregoing detailed description has set forth
several exemplary embodiments of the apparatus and methods of the
present invention, it should be understood that the above
description is illustrative only and is not limiting of the
disclosed invention. It will be appreciated that the specific
dimensions and configurations disclosed can differ from those
described above, and that the methods described can be used within
any biological conduit within the body.
* * * * *