U.S. patent application number 09/944200 was filed with the patent office on 2002-05-30 for method of treating a body vessel or duct with radiation from within the lumen.
Invention is credited to Bradshaw, Anthony J., Edison, John P., Raizner, Albert E., Weinberg, Steven L..
Application Number | 20020065448 09/944200 |
Document ID | / |
Family ID | 22009886 |
Filed Date | 2002-05-30 |
United States Patent
Application |
20020065448 |
Kind Code |
A1 |
Bradshaw, Anthony J. ; et
al. |
May 30, 2002 |
Method of treating a body vessel or duct with radiation from within
the lumen
Abstract
A method is disclosed to treat the wall of a blood vessel from
within the lumen thereof with a radiation catheter that includes a
working or radiotherapy lumen, a longitudinally channeled distal
balloon, and a balloon inflation lumen. The method includes steps
of inserting the catheter into the vessel lumen until the balloon
is adjacent a target site of the vessel wall to be treated,
inflating the balloon to substantially center the catheter
radiotherapy lumen within the vessel lumen at the target site while
allowing perfusion of blood past the inflated balloon through
channels formed by the balloon, advancing a radioactive source into
the catheter radiotherapy lumen to position the source within a
region of that lumen along a portion of the catheter occupied by
the balloon; and withdrawing the source after it has been
positioned within that region of the radiotherapy lumen for a
predetermined interval of time.
Inventors: |
Bradshaw, Anthony J.;
(Missouri City, TX) ; Weinberg, Steven L.; (League
City, TX) ; Raizner, Albert E.; (Houston, TX)
; Edison, John P.; (Houston, TX) |
Correspondence
Address: |
BLANK ROME COMISKY & MCCAULEY, LLP
900 17TH STREET, N.W., SUITE 1000
WASHINGTON
DC
20006
US
|
Family ID: |
22009886 |
Appl. No.: |
09/944200 |
Filed: |
September 4, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09944200 |
Sep 4, 2001 |
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08644101 |
Feb 7, 1996 |
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08644101 |
Feb 7, 1996 |
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08057322 |
May 5, 1993 |
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Current U.S.
Class: |
600/3 |
Current CPC
Class: |
A61N 2005/1003 20130101;
A61M 2025/1047 20130101; A61N 5/1002 20130101; A61B 2017/22002
20130101; A61M 2025/0183 20130101; A61M 25/1002 20130101; A61N
5/1007 20130101; A61N 2005/1025 20130101 |
Class at
Publication: |
600/3 |
International
Class: |
A61N 005/00 |
Claims
What is claimed is:
1. A source wire for treating tissue within a patient's body by
localized in vivo radiation of tissue at a target site from a
radioactive source of the source wire, the source wire being
introducible by applicator to the target site via an implanted
catheter or a natural vessel, duct or chamber of the patient's body
that provides a pathway or portion of a pathway to the target site
from a point external to the body, said source wire comprising: an
elongate wire composed of nickel-titanium alloy, having preselected
properties of flexibility, springiness, slipperiness, mechanical
strength and shape memory retention, said elongate wire having a
proximal end and a distal end, and a radioactive source assembled
with said elongate wire at the distal tip thereof for delivery
through said pathway to the target site by loading and advancing
the elongate wire along the pathway from the proximal end of the
elongate wire, until the source is disposed at the target area for
irradiating the selected tissue.
2. The source wire of claim 1, wherein: the elongate wire is a
solid lead of substantially uniform thickness along its entire
length.
3. The source wire of claim 1, wherein: the elongate wire is a
cable composed of a multiplicity of strands of substantially
uniform thickness throughout the entire length of each strand, each
strand having a distal end and a proximal end.
4. The source wire of claim 3, wherein: the distal end of at least
some of the strands is set back relative to the distal end of the
elongate wire and to the distal end of other strands of the cable,
to form a taper that narrows from a point short of the distal end
of the wire to the distal end of the wire, for ease of entry into
portions of the pathway of reduced size.
5. The source wire of claim 2, wherein: the elongate wire has an
axial hole of predetermined depth at its distal tip, the source is
disposed in said axial hole, and a plug is fastened to the distal
tip of the elongate wire to seal said axial hole with the source
disposed therein.
6. The source wire of claim 5, wherein: the source comprises an
iridium isotope that has been irradiated to a predetermined
radioactivity level for treatment of the tissue in the target
area.
7. The source wire of claim 6, wherein: the source comprises a
plurality of segments of said iridium isotope.
8. The source wire of claim 6, wherein: the iridium isotope has a
radioactivity level of at least one curie.
9. The source wire of claim 6, wherein the tissue to be treated is
a malignant tumor, and the iridium isotope source has a
radioactivity level of approximately 10 curies.
10. The source wire of claim 9, wherein: the elongate wire has a
diameter less than approximately 0.028 inch.
11. The source wire of claim 6, wherein the tissue to be treated is
an interior surface of a vascular wall which has been subjected to
trauma by prior treatment to reduce the presence of plaque, and the
iridium isotope source has a radioactivity level in the range of
approximately 1 to 2 curies.
12. The source wire of claim 11, wherein: the elongate wire has a
diameter less than approximately 0.021 inch.
13. The source wire of claim 1, wherein: the elongate wire is an
assembly of a tube and a solid backbone wire running the entire
length of the tube except for a displacement of the end of the
backbone wire relative to the same end of the tube to form an axial
hole of predetermined depth to accommodate radioactive source
material therein, and a plug fastened over the open end of the
axial hole to securely seal the source material therein.
14. A method of treating smooth muscle cell tissue within the body
of a patient, using a radioactive source wire, comprising the steps
of: implanting a catheter in the patient to provide a pathway from
a point external to the patient's body to a point at or near a
predetermined target area about the patient's heart for the tissue
to be treated, advancing a source wire including an elongate lead
having a distal end with a radioactive source thereat and a
proximal end from which the source wire is advanced, through the
catheter by limiting the elongate lead to a sufficiently small
diameter to carry the radioactive source to the immediate vicinity
of the tissue for irradiation thereof in the target area, having
selected the elongate lead to be sufficiently flexible and
mechanically strong to traverse the catheter without substantial
kinking while resisting breakage, halting the advance of the source
wire through the catheter when the distal end reaches the point at
which the source wire is to irradiate tissue in the target area,
irradiating the targeted tissue for a predetermined interval of
time, and withdrawing the source wire from the catheter immediately
upon completing the irradiation of tissue for the duration of the
interval.
15. The method of claim 14, wherein the target area is a coronary
artery, and further including: centering the distal tip of the
source wire in the coronary artery to produce subtantially uniform
irradiation of the radioactive tissue adjacent the source,
16. The method of claim 15, further including: performing the
irradiation substantially immediately after the coronary artery has
been subjected to opening of the lumen by reduction of the
thickness of plaque on the interior surface of the wall of the
artery, to produce subtantially uniform irradiation of the
radioactive tissue adjacent the source, and thereby reduce the
likelihood of restenosis of the irradiated interior surface of the
artery wall.
Description
BACKGROUND OF THE INVENTION
[0001] The present invention relates generally to radioactive
sources used for treatment of tissue in the human body. More
particularly, the invention resides in a device, apparatus, and
methods for treating tissue by irradiation with a predetermined
dose from a radioactive source which is delivered into the body of
the patient via a natural or artificial pathway for a very brief
treatment interval or fractionated treatment sessions. The device,
apparatus and methods of the invention are especially well suited
for brachytherapy in which a malignant tumor is exposed to
localized in vivo radiation from a pathway within or adjacent the
tumor site, or for controlled irradiation of the wall of a blood
vessel, particularly coronary arteries or related blood-carrying
canals, to condition the interior surface thereof against
restenosis.
[0002] Brachytherapy, a technique for radiation treatment of
malignant tumors, attacks the tumor from within the body. The
method typically utilizes a radioactive source wire in which a
radioisotope sealed at and substantially integral with the distal
tip of a relatively thin wire or cable is delivered via a pathway
formed by a catheter or through a natural cavity, duct or vessel of
the body directly to the tumor site for localized irradiation. One
or more catheters, for example, may be implanted in the patient's
body to provide the pathway(s) from a point external to the body to
and through the tumor site, so that the interior of the tumor mass
is accessible via the catheter(s). The radioactive source, with a
dose that may range from about one curie to about ten curies, is
mechanically delivered to the site either by hand feeding the
source wire (for low dose and more readily accessible tumor sites)
or by means of apparatus known as an afterloader which has a drive
system to which the proximal end of the source wire is
connected.
[0003] Usually, the treatment is fractionated, in that repeated
short intervals of treatment are performed, with the source wire
being introduced for the irradiation, left in place for the
predetermined interval prescribed by the attending oncologist
(often after consultation with a physicist who has calculated the
size of the tumor, the distance to be traveled by the source, the
nature of the pathway to be traversed and likely travel time, and
other pertinent factors), and then withdrawn into the afterloader's
shielded safe. To permit treatment to be performed through multiple
catheters to the tumor site, if deemed appropriate by the
oncologist, the afterloader may be provided with a turret for
automatic delivery of the source wire in succession to the entry
points of the several catheters for automated advancement,
treatment and withdrawal in each pathway. The desired treatment
time in each case is programmed into the afterloader's control
unit.
[0004] The treatment regime may be repeated at regular intervals
over a period of many days, weeks or months, and, if successful,
results in complete destruction or at considerable shrinkage of the
tumor(s). Among the advantages of this type of radiation therapy
are exposure of the tumor to fractionated treatment doses of
localized radiation so that each individual treatment need only be
of extremely short duration to provide the desired effect while
reducing the extent of patient exposure and discomfort, and to
provide relatively rapid shrinking of the tumor while avoiding
prolonged exposure of healthy tissue to radiation.
[0005] Because this type of therapy is more applicable to
inoperable malignancies deep within the body, the site of the
tumor(s) is usually difficult to reach as the source wire is guided
through the path provided by the implanted catheter. The catheter
itself may be positioned in place using a previously implanted
guidewire or "rail" over which it is advanced along a lumen
distinct from the lumen of the catheter through which the source
wire is advanced and retracted. It is often the case that this
pathway is long, extremely narrow and tortuous with numerous bends
and turns. It is essential, therefore, that the source wire should
be suitably thin, strong and flexible to traverse the pathway.
Furthermore, the wire must be adapted to carry a suitably sized
radioactive source, i.e., the core which, for high dosage
treatments, is typically substantially pure iridium processed in a
neutron flux to produce the radioactive isotope Ir-192. Hence, the
source wire has the conflicting requirements that it be of
sufficiently small diameter and flexibility to traverse the path to
and from the tumor, sufficiently strong along with its flexibilty
to be driven through the pathway without binding or kinking during
wire advancement, and with the capacity to deliver a radiation
dosage of as much as ten or more curies.
[0006] Prior art source wires include cable composed of a
multiplicity of tiny strands of stainless steel wire to provide
both desired strength and flexibility, but which lack the size or
diameter to travel through the smallest sizes of pathways required
for brachytherapy treatment of certain tumors, such as in or
through the biliary tract or the bronchi of the lungs. Also, cable
source wires typically require welding a plug or capsule containing
the radioactive source to the distal tip, which creates a point of
weakness where fracture may occur. It is imperative, of course,
that the source wire be sufficiently sound and reliable to avoid
even the remote possibility that it may break and cause the
radioactive material portion to be left in the patient's body for a
protracted interval of time.
[0007] Solid source wire is capable of accommodating the Ir-192 or
other source material in a hole formed in the distal tip of the
wire to provide better sealing and security of the source material.
Also, solid source wire can be produced by specialized techniques
in sizes ranging down to from about 0.6 to 0.7 millimeter (mm)
diameter to accommodate an Ir-192 source having a dosage or
radioactive level or strength of up to about 10 curies. Other
conventional source materials include cobalt, cesium, palladium,
gold, and iodine. The source wire may be composed of stainless
steel, platinum or certain other conventional materials of suitable
flexibility.
[0008] For low dose sources in particular, such as one curie or
slightly higher, the source material may be installed and the
entire source wire then subjected to processing in a nuclear
reactor to impart the desired level of radioactivity to the source
material. This is an acceptable procedure where the half-life of
the wire material is considerably less than that of the source
material, so that the radioactivity of the wire material itself is
sufficiently dissipated to permit it to be used within a few days
after activation. Platinum wire, for example, is suitable for that
purpose. For higher dose sources, the source material alone is
subjected to the neutron flux and subsequently assembled in the
wire by means of shielded, remotely controlled handling and
manipulating techniques.
[0009] Recently, it has been found that radioactive irradiation of
the interior wall surface of blood vessels in general and the
coronary arteries in particular with a low dose source for a very
brief interval following treatment of the vessel for removal or
compression of occluding material such as plaque, enjoys marked
success in preventing restenosis. Restenosis is a recurrence of the
stricture or narrowing of the vascular lumen or heart valve
following surgery or other treatment for removal or reduction of an
occlusion, or from related trauma. For example, cardiac patients
who have been treated by balloon angioplasty, artery interior wall
scraping, laser removal of plaque, by-pass surgery, and other
conventional techniques for treating stenosis or occusion of the
blood vessels either because of or in avoidance of myocardial
infarction, have been found to experience high incidence of
restenosis.
[0010] Approximately one-third of the patients who have had
arteries unblocked suffer restenosis about six months later,
requiring that the procedure be redone. And in fact, repeating the
procedure appears to increase the trauma to the smooth muscle cells
and to speed their regrowth. Fifty percent of the patients
experience some form of reocclusion of the treated vessel. While a
repeat procedure may not be required for all of those patients,
some reocclusion does occur. The remaining 50% of the patients seem
to suffer no reocclusion, and there is no single explanation for
it.
[0011] The fact that one-third of all patients require retreatment,
at substantial additional cost and with potential loss of life
raises questions concerning the significance of a 95% success rate
for the initial unblocking procedure. Moreover, if a second
reocclusion occurs, the next procedure performed on the patient is
likely to be open heart surgery.
[0012] Restenosis, then, is really an injury response mechanism to
the unblocking procedure, at least for some subtantial percentage
of the patients. Attempts to correct the restenosis problem by use
of drugs have not been successful.
[0013] Irradiation of the vessel wall with a radioactive source
appears to alleviate the problem in tests conducted on rabbits and
rats, but creates a new problem in that the source wire must be
sufficiently thin, flexible and strong to be capable of placement
in the offending arteries. This is by no means a simple task,
because of the small size of the vessels, the difficulty in
reaching the target area through the artery as a consequence of the
small size of the target and the tortuous pathway involved, and
especially the susceptibility of the patient to a heart attack if
the critical vessel is blocked for an inordinate time during
performance of the treatment.
[0014] The problems involved are similar to, if not greater than,
those encountered in treatment of tumors by brachytherapy as
described above. It is a principal object of the present invention
to provide new and improved source wires, apparatus and methods for
in vivo, localized, internal radioactive treatment of selected
tissue in the human body.
[0015] The cost of treatment for heart attack victims is
staggering, and is among the procedures being addressed in a strong
effort toward cost containment by treatment centers and other care
providers. Of course, if treatment is unsuccessful, inadequate or
untimely, the cost is even greater--in loss of life. Therefore, it
is another important object of the present invention to provide
improved and lower cost means and methods for treating cardiac
patients to avoid restenosis of the veins and arteries, and even of
the heart valves, following procedures used to open a blocked or
partially blocked or inoperative blood passageway.
SUMMARY OF THE INVENTION
[0016] According to the present invention, a new and improved
radioactive source wire is provided for use both in brachytherapy
and cardiac treatment for the purposes described above. In
particular, the source wire is composed of a nickel-titanium alloy
known commercially as nitinol which has the desired properties of
flexibility, springiness, slipperiness, mechanical strength and
super-elasticity, and which returns to a straight shape after it is
withdrawn from the narrow tortuous pathway through which it was
driven for purposes of treatment. The radioactive source material,
such as Ir-192 (iridium isotope) spheres, is loaded in an axial
hole in the distal tip of the wire, which is then sealed with a
nitinol plug as by welding. The nitinol source wire is readily
returned to the drive system of the afterloader without likelihood
of kinks or bends, for subsequent use in another or other
procedures of the same type.
[0017] The wire is composed of a shape memory alloy, the
nickel/titanium alloy nitinol being preferred, possessing
super-elastic properties and the capability, at proper temperature,
of transforming from an unstressed austenitic state (being a
straight configuration) to a stress induced martensitic state and
the capability of returning to the austenitic state when the
externally induced stress is removed. The deformations encountered
in tortuous pathways are fully recovered without permanent plastic
deformation, and the material transforms to the stable austenitic
state for storage or spooling with no permanent deformation from
the prior use.
[0018] Nitinol has been used commercially in bendable frames for
lenses (eyeglasses). It has also been used in the past for rails
(guidewires) that are employed in various parts of the body by
placement through a lumen to define a selected site as a means to
transport and retrieve items to and from that site. In this way,
the rail dispenses with the need to relocate the the selected site
repeatedly, such as for placement of catheters. However, to our
knowledge, there has been no suggestion that nitinol would serve a
useful purpose as a source wire for radioactive source
material.
[0019] The procedure for which the nitinol source wire is used may
be a brachytherapy application or a coronary radiotherapy
application. The same basic afterloader drive system is used for
both applications, although the machines themselves are somewhat
different. For example, the brachytherapy (oncology) afterloader is
more complex only because of the large variety of targets (tumors
at sites possibly anywhere in the body, versus targets at or in the
region of the heart for the coronary machine), and up to about 20
channels versus only one channel required for the coronary
radiotherapy machine. The radioactivity shielded safe is larger on
the oncology machine because the source is of greater radioactivity
level. Also, in the coronary machine it is not necessary to use a
turret, or at maximum, a two-position turret, whereas the turret of
the brachytherapy afterloader has a number of positions
corresponding to the array of channels available for delivery of
treatment. The basic structure of each machine may be entirely
conventional.
[0020] In the coronary radiotherapy treatment procedure of the
invention, the afterloader equipment is adapted to advance a dummy
wire (non-radioactive) through the implanted catheter to the target
site under visual observation such as fluoroscopy, after which the
dummy wire is retracted, and the source wire is then automatically
advanced to the target site through the catheter for localized
irradiation of the vessel wall over a very brief period of time
that depends on the radioactivity dosage prescribed by the
attending physician. The dummy wire has an opaque tip marker to
facilitate the fluoroscopic observation, and the precise location
of the target area along the pathway is calibrated in the
afterloader according to the measured distance of travel by the
dummy wire. The treatment is performed automatically by remote
operation of the afterloader which is located in a
radiation-shielded room where the patient is placed for the
treatment.
[0021] A treatment catheter is coupled to the end of the
afterloader connector and deployed over a rail guidewire to the
target site for ultimate delivery and retraction of the radioactive
source. In the case of coronary radiotherapy, the source material
in the source wire must be centered to provide uniform irradiation
to achieve maximum results. A non-centered source could deliver too
little radiation to one side of the artery interior wall, resulting
in no effective treatment of that region, and too much to the other
side, resulting in possible injury to that portion.
SUMMARY OF THE DRAWINGS
[0022] The above and still further objects, features and attendant
advantages of the present invention will become apparent from
consideration of the following detailed description of certain
presently preferred embodiments and methods of the invention, taken
in conjunction with the accompanying drawings, in which:
[0023] FIG. 1 is a simplified view of a typical arrangement for
implementing a procedure with a brachytherapy system or a coronary
radiotherapy system according to the present invention;
[0024] FIG. 2 is a fragmentary, perspective view of a catheter,
rail, and source wire connected at the proximal end to the
afterloader drive connector;
[0025] FIG. 3 is a simplified side view of the system of FIG.
2;
[0026] FIG. 3A is a sectional view through the lines A-A of FIG. 3;
and
[0027] FIG. 4 is a fragmentary sectional side view of the source
wire showing an exemplary assembly of the radioactive source
material and special wire material according to the invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT AND METHOD
[0028] Referring to FIG. 1, the invention in one of its aspects is
used in treatment regimens provided by a brachytherapy system or a
coronary radiotherapy system. In practice, the patient 10 is moved
into a radiation-shielded treatment room where the procedure will
be performed. A treatment catheter 12 is implanted in the patient,
and, in the coronary or cardiac procedure is also coupled to a
connector of the drive system for the remote afterloader 15. The
drive system, and indeed, the entire afterloader may be completely
conventional for the brachytherapy application, and would require
only a few chnages for the cardiac application.
[0029] It will be understood that while both uses are described in
this specification, in the typical case, the patient will go
through only one of the two procedures. Also, separate afterloaders
and treatment rooms would be provided for the two different
applications. The decription of both procedures here is solely for
the sake of convenience, and because many aspects of the present
invention are applicable to both types of treatment.
[0030] For treatment, the patient 10 is placed in a supine or a
prone position on a table 17, with the afterloader 15 placed in
close proximity to allow the source wire of the afterloader to be
deployed through the treatment catheter into the selected target
site in the patient's body. The afterloader is controlled by the
attending physician, an oncologist in the case of brachytherapy
treatment or a cardiologist in the case of cardiac treatment,
and/or by a radiotherapist 20 from a control console 22. In
practice, the control console may be in the treatment room where
low dose radioactivity treatment is being performed, but shielded
with the attendant by a set of radiation screens 25, or may be
located outside the shielded treatment room for high dose
radioactivity treatments.
[0031] A fluoroscope 28 is positioned above the patient, although
its use would usually be required only for the cardiac treatment. A
video camera and display monitor 30 are positioned to allow
attendant 20 to view the patient, with equipment including display
controls 31 positioned within easy access to the attendant.
[0032] The method used in performing brachytherapy is entirely
conventional, and hence, only portions of it will be described here
in those portions of the text where appropriate. Description of the
method and certain specialized apparatus employed for the cardiac
treatment will be described presently. First, however, it is
desirable to describe aspects and features of the preferred
embodiment of a source wire which, except for radioactive dosage
requirements, may be used for either procedure.
[0033] According to the preferred embodiment of the invention, the
source wire is an assembly of an elongate wire composed of a
nickel/titanium alloy commercially marketed as nitinol. Nitinol is
available, for example, from Shape Memory Alloys of Sunnyvale,
Calif. The material is described, for example, in U.S. Pat. No.
4,665,906. For purposes of the source wire application according to
the invention, the nitinol in the form of a wire is stored in its
austenitic state (below the transition temperature, discussed
below), characterized by a straightened shape, and when used is
flexed to put it in a stress-induced martensitic state (above the
transition temperature), which is characterized by
super-elasticity. When the wire is formed, the process, which
involves several separate treatments at high temperature, produces
a transition temperature of the material between its austenitic
state in which it is ductile, to the stress-induced martensitic
state. In source wire of the invention, the nitinol is always used
for treatment at a temperature above the transition temperature,
which is typically 15.degree. C..+-.5.degree. C., for example, and
is in the austenitic state except when the wire is in flexation at
which it is in the stress-induced martensitic state. This is the
case for the nitinol wire used in either of these applications,
where it is bent and flexed as it moves through a tortuous path in
the human body in the brachytherapy treatment or cardiac treatment
procedure.
[0034] The transition temperature may be varied somewhat as a
function of the manner in which the nitinol wire is processed,
especially its heat treatment. For example, in one form in an
austenitic state the wire material was floppy, which did not
adversely affect cycling tensile strength or shear strength. In the
preferred form the nitinol wire has a sufficient memory aspect to
retain straightness despite a capability to be
[0035] For purposes of assuring retention of its desired properties
in that state, such as the properties of high flexibility,
springiness, slipperiness and mechanical strength, the nitinol wire
is heat treated while it is being processed to form wire of the
desired diameter for use in the brachytherapy and coronary
radiotherapy applications of the invention. As with stainless steel
rods and wires, nitinol can be drawn and successively redrawn to
progressively smaller diameters.
[0036] Because the manufacturing process can affect the wire's
properties, it is important to verify metallurgical specifications
as part of the testing of the wire for performing validations,
including basic factors such as ultimate tensile strength. Cycling
of the wire (i.e., putting it through tests in which it is used and
reused in the intended manner for the application) is important to
detect otherwise unseen characteristics that may adversely affect
its performance, such as case hardening due to grinding, and to
assure absence of lot-to-lot variations.
[0037] Three different processes were employed to produce the
nitinol wire for use in source wire according to the invention. It
was necessary both to produce the wire in its final form (i.e.,
dimensional including diameter and length) and to provide it with a
cavity in which radioactive source material would be retained. In
particular, an axial hole is formed at the distal end of the wire
to house the source material, which would subsequently be sealed to
prevent particulate loss and contamination.
[0038] One process of producing the wire with an axial hole at its
tip involved drilling a hole in an oversize wire or rod, followed
by repeated drawing of the wire through progressively smaller dies
until the desired wire diameter and hole depth were achieved.
During the drawing stages the depth of the hole underwent
lengthening, as would be expected, so it is necessary to calculate
the desired final depth and from that, determine the depth of
initial drilling of the hole. Wire diameter of 0.023 inch and hole
diameter of 0.014 inch is preferred. This hole drilling and drawing
process to provide the final form of the wire and desired
properties was performed for the assignee of the present
application by the Raychem Corporation of Menlo Park, Calif.
[0039] A second process, also performed by Raychem Corporation,
produced a similar form of wire which constitutes a thin-walled
nitinol tube clad over a nitinol backbone wire running
substantially the entire length of the tube except for a portion at
the tip. This portion provides the hole of desired depth to house
the source material. Other dimensions of the tube/backbone wire are
substantially the same as those described above for the drilled
hole/drawdown version of the wire. A slightly greater outer
diameter of 0.022 inch resulted from this process.
[0040] A third process, which was used only to produce the axial
hole in the tip of a nitinol wire of the final desired diameter,
involved the use of electrical discharge machining (EDM) performed
by Mega Technology EDM, Inc. of Norcross, Ga. In contrast to the
other processes, the EDM process has tended to produce a hole wall
of somewhat varying thickness. In any event, however, the EDM
process did produce a hole of desired diameter and depth in the end
of the wire without need for further drawing.
[0041] A fragmentary portion of the final source wire is shown in
the side sectional view of FIG. 4. The nitinol elongate wire 38
with axial hole 39 in its distal tip is loaded with radioactive
source material such as iridium isotope Ir-192 spheres 40 of
slightly smaller diameter than that of the hole 39. The
radioactivity level of the total source material in the wire is
preferably about one to two curies (a low dose wire) for the
cardiac application, and from that dose up to about 10 curies (a
high dose wire), depending on physician-prescribed dosage, for the
brachytherapy application.
[0042] After loading the source material, a nitinol plug 42 of
preferably rounded shape is inserted into hole 39 to tightly cap
it. The plug is then welded to seal the hole against loss of any
source material. The source material may be enriched Ir-192, and in
any event is substantially pure iridium converted to radioactive
form by treatment in a nuclear reactor in a known manner. The
radioactive spheres are assembled in the nitinol wire and the hole
is sealed with the welded plug by manipulations performed using
remote manipulators in an assembly area.
[0043] A feature of the preferred embodiment of the source wire is
that it may be tapered down at the distal end to provide even
greater flexibility in reduced size at the point of delivery of the
dosage to the target which is to be irradiated. A somewhat larger
diameter of the wire up to the point at which the taper begins is
useful to provide the column strength sufficient for drivability of
the wire by the afterloader. For example, in the embodiment of FIG.
4 the distal end 45 of the wire may be tapered over the last six
inches to the tip, by drawing that portion through an appropriately
sized die. The tapering process would be performed prior to loading
radioactive source material.
[0044] If a multi-strand cable were used in place of a solid wire
for the source wire, the cable can similarly be tapered. This is
accomplished by tapering every strand at the distal end, so that
when the strands are is twisted to produce the final form of the
cable, it has a rat-tail shaped taper. Although it is not the
preferred mode of a source wire, the multi-strand cable form may be
assembled with a small capsule containing the radioactive source
material, by welding the capsule to the distal tip of the cable.
Each strand may have an extremely small cross-section, e.g., 0.001
inch, so that it bends easily, making the overall cable very
flexible. Such cables have been produced without taper in stainless
steel, but a form used in accordance with the present invention
would employ nitinol strands.
[0045] By way of comparison, a nitinol solid wire has almost twice
the column strength of a multi-strand stainless steel cable of
corresponding diameter. Multiple strand cable ordinarily has a
slight advantage in flexibility, but the nitinol material tends to
reduce that advantage by virtue of its flexibility, even as a solid
lead. Such flexibility is especially important in the applications
described herein. Insufficient flexibility can cause the wire to
develop small kinks as it travels through curves in the catheter,
and the kinks become of greater width in any short section of the
wire than the width of the catheter lumen. Consequently, the wire
will lock in the catheter, perhaps so much so that it becomes
immovable in either direction. This is completely unacceptable
where a radioactive source wire is being used.
[0046] In the method of the invention, a treatment catheter 12
(FIGS. 1, 3) is implanted in the patient to provide the pathway to
be traveled by the source wire, and the wire is advanced (or
withdrawn) in that pathway through the catheter during the
treatment procedure, whether for brachytherapy or for coronary
radiotherapy. Of course, the selected target is different depending
upon application.
[0047] In the cardiac application, the catheter is also coupled to
the afterloader connector 50 by a guidewire or rail 52 which
extends to the target site. The catheter for that application may
be provided with small channels to allow some blood flow
therethrough. The catheter 12 is placed over the rail 52 which is
hooked into the connector for the afterloader as well. The
afterloader connector 50 is also coupled to the turret. A key 55 is
used to lock the coupling in place and prevent the catheter and the
rail from undergoing rotation.
[0048] Since the rail lumen 58 (FIG. 3A) is at the top of catheter
12, the key 55 on the afterloader coupling 50 locks the catheter
against rotation. If the catheter were allowed to rotate, the rail
(guidewire) 52 would begin uncontrollable spinning because of the
eccentricity of its lumen 58 in the catheter. Orientation of the
guidewire channel is also extremely important, and is maintained by
the key.
[0049] The cardiac application of the radioactive source wire is
extremely size sensitive. Among critical issues for that
application are flexibility for access through the fine and
tortuous pathways to the very fine and remote blood vessels, and
size for entry into the vessels.
[0050] A suitable level of radioactivity (dosage) for the source in
this application is one curie, and such a source would be kept in
place a period sufficient to produce, say, 1,000 to 1,500 rads at
one millimeter distance from the vessel or valve wall.
Radioactivity delivered to the wall surface depends on factors such
as the length of source, the length of the lesion and the curie
level on the day the treatment is performed, and the length of time
of the treatment.
[0051] The patient can only tolerate one to one and a half minutes
of total occlusion in the target area, which means that the
treatment must be stopped before the limit is reached, the
attending personnel then return, the balloon is deflated to allow
the heart (or the portion being treated) to reoxygenate. After an
interval of, say, three to five minutes, the treatment procedure is
recommenced to apply the remaining dosage required to irradiate the
target area by redeployment of the source wire and the centering
balloon.
[0052] It is also imperative to provide centering of the wire in
the vessel, although somewhat less so with a small diameter artery
because, for example, one side may be 21/2 mm and the other may be
2 mm. The need to center exists to avoid a hot spot on one side.
Preliminary results also indicate that a failure to obtain a
certain threshold of radiation on the vessel wall, about 1,000
rads, will result in no discernible prevention of restenosis.
[0053] In the preferred embodiment, an inflatable balloon is
provided in the catheter for centering the source tip of the source
wire. A dose of 1,000 to 1,500 rads drops off according to the
inverse square of the distance, so that a distance of 5 mm from the
vessel wall to the source (atually the tip of the source wire),
causes the field strength to drop off sharply, with concomitant
loss of threshold. The treatment catheter may include, in addition
to the working treatment (radiotherapy) channel, the rail
(guidewire) channel, an inflation channel for the centering
balloon. Segmented or scalloped balloons, or otherwise channeled
balloons may be used, together with a channeled catheter or alone,
to permit some flow-by of blood sufficient to avoid complete
blockage during treatment.
[0054] For treatment at the bottom of the heart, a scalloped
catheter with no balloon is preferred. In that situation, centering
of the source within that treatment area with some blood flow-by
capability is achievable without need for a balloon.
[0055] A different type of centering mechanism may be used, and in
that event could be of a type and shape that would permit
sufficient blood flow so that the procedure need not be stopped
before the treatment regimen is completed. The problem of using a
different mechanism is principally in the means for deployment.
Balloon inflation and deflation in a catheter is in and of itself
an entirely conventional technique and has a proven record of
safety.
[0056] The irradiation procedure is preferably performed very soon
after the balloon angioplasty (PTCA) or other unblocking procedure
is completed on the vessels. The rail (guidewire) is left in place
during the period of treatment because it allows a rapid return to
the target. Since the rail is tiny, at 0.014 inch, it does not
seriously impede blood flow. Initially, the rail is steered into
the part of the heart being targeted, using a fluoroscope, becomes
the first component in and the last out.
[0057] If not installed properly, a branching effect can occur.
Thus, the catheter and subsequently the source wire must be
advanced to the desired branch via the rail. The catheter is placed
over the rail, and in available size ranges, is capable of moving
through vessels or ducts as small as two mm in diameter.
[0058] Lumen diameter of the artery dictates the choice of
treatment catheter as well as the radioactivity dose. If it is
determined that the dose should be 1,450 rads, for example, that
value is entered on the control console of the afterloader, or
other factors may be entered by which a microprocessor in the
control console may calculate the dose according to location of the
target, size of lumen, center of the lumen (distance to the
interior wall surface), curie rating per day, and other known
factors.
[0059] A fail-safe function of the afterloader senses patient
problems when the coronary radiotherapy is administered. In the
event that the patient is experiencing pain or other difficulties,
the source wire is promptly drawn back and the balloon is deflated
and the patient's heart is allowed to reoxygenate. The target
location is marked with a dummy wire deployed from the afterloader.
The control console of the afterloader enables programming of the
desired functions. A one to one and one-half minute interval is
timed by the afterloader, the procedure halted at that point, the
source wire is retracted into the safe. The afterloader retains all
necessary data such as the dose given and the dose given on transit
to and from the point at which initiated, or transit dose, and
treatment is recommenced after a break of two or three minutes.
[0060] Although a preferred embodiment and method of the present
invention has been described herein, it will be apparent from the
foregoing description to those skilled in the field of the
invention that variations and modifications of the invention may be
implemented without departing from the spirit and scope of the
invention. Accordingly, it is intended that the invention shall be
limited only to the extent required by the appended claims and the
rules and principles of applicable law.
* * * * *