WO1998034681A1

WO1998034681A1 - Apparatus and method for intravascular radiotherapy

Info

Publication number: WO1998034681A1
Application number: PCT/US1998/002790
Authority: WO
Inventors: Anthony J. Bradshaw; Steven L. Weinberg; Albert E. Raizner; John P. Edison
Original assignee: Guidant Corporation
Priority date: 1997-02-07
Filing date: 1998-02-09
Publication date: 1998-08-13
Also published as: AU6325098A

Abstract

A source wire (38) having a radioactive source (40) at its distal tip (45) is used to treat a blood vessel within a patient's body by localized in vivo radiation to prevent stenosis of the blood vessel, including restenosis following percutaneous transluminal coronary angioplasty. The source wire (38) is advanced to the target site along the vascular system of the patient's body from a point external to the body. The source wire (38) is preferably a solid lead of substantially uniform thickness along its entire length, composed of a super-elastic nickel-titanium alloy (nitinol). Alternatively, the wire (38) may be a cable composed of multiple strands of the alloy of substantially uniform thickness throughout the entire length of each strand. The alloy has desired characteristics of super-elasticity for transitioning into and out of a stress-induced martensitic state as it is advanced through tortuous lumens for passage into the coronary arteries.

Description

APPARATUS AND METHOD FOR INTRAVASCULAR RADIOTHERAPY

Cross-Reference to Related Application

This application is a continuation-in-part of co-pending application Serial No.

08/467, 7iι filed June 6, 1995, for Radioactive Source Wire, Apparatus and Treatment

Methods, by the same inventors.

Background of the Invention

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.

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 rhass is

accessible via the catheter(s). The radioactive source, with an activity level in a range up to

about ten curies, is delivered to the site either manually by hand feeding the source wire (generally limited to low level radioactivity and with respect to the more readily accessible

tumor sites) or in automated manner by means of apparatus known as an afterloader which has

a drive system to which the proximal end of the source wire is connected.

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 a shielded safe of the afterloader. 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. The treatment regimen may be repeated at regular intervals over a period of

many days, weeks or months, and, if successful, results in complete destruction or at least

considerable shrinkage of the tumor(s). This type of radiation therapy has the advantage of

fractionated treatment of the tumor with localized radiation in small doses of extremely short

duration per individual treatment to reduce patient discomfort, while still effecting relatively rapid shrinkage of the tumor without prolonged exposure of healthy tissue to radiation.

This type of therapy is particularly suitable for treating inoperable malignancies located deep within the body, with consequent difficulty of access to the tumor site, so that

the source wire is guided along a path to the site provided by an implanted catheter. The

catheter may be positioned in place using a previously implanted guidewire or "rail" over which

it is advanced, and thereafter the source wire can be advanced and retracted along a lumen of

the catheter. Typically the pathway to the site is long, extremely narrow and tortuous with

numerous bends and turns. It is essential, therefore, that the source wire be sufficiently thin

(i.e., small diameter), strong, and flexible to be driven through the pathway to and from the

target site without binding or kinking during wire advancement. Additionally, the wire must

be capable of carrying a radioactive source or core such as substantially pure iridium which has

been activated in a neutron flux to isotope Ir- 192 having suitable relatively high activity level (e.g., ten or more curies) for tumor treatment.

One prior art source delivery device comprises a cable fabricated from a

multiplicity of tiny strands of stainless steel wire which provide desired strength and flexibility.

However, such cables generally have a diameter which precludes travel through the narrowest pathways required to be traversed for delivering brachytherapy treatment to certain tumor sites,

such as in or through the biliary tract or the bronchi of the lungs. Also, the radioactive source

is typically carried in a capsule welded to the distal tip of the cable, which creates a point of

weakness where fracture may occur during use of the device. It is imperative that the delivery

member be sufficiently sound and reliable to avoid even a slight possibility of breakage that

would result in radioactive material being left in the patient's body for a protracted period.

A 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, for better sealing and securing of the source. Also, a solid wire can be produced by specialized techniques to have a diameter as

small as from about 0.6 to 0.7 millimeter (mm), and still accommodate an Ir-192 source having

a radioactivity level 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.

For low activity sources in particular, such as one curie or slightly higher, the

source material may be installed in the wire 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 activity 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.

Recently, it has been found that irradiating the interior wall surface of blood vessels in general and the coronary arteries in particular with a low activity source for a very brief interval following treatment of the vessel for removal or compression of occluding,

clogging, or blocking material such as plaque, may have merit in preventing restenosis of the vessel. Restenosis is a recurrence of the stricture or narrowing of the vascular lumen following

surgery or other treatment for removal or reduction of an occlusion, or from related trauma.

For example, cardiac patients treated with balloon angioplasty, scraping or laser treatment of

the internal surface of an artery wall for compression or removal of plaque, or subjected to by¬

pass surgery, or to other procedures for opening the lumen of a blood vessel, have been found to experience high incidence of restenosis.

Approximately one-third of such patients suffer restenosis within a period of

about six months after the procedure, necessitating a repeat procedure which, while temporarily

opening the vessel lumen, appears to exacerbate the trauma and to result in further proliferation

of smooth muscle cells that cause blockage. Inexplicably, the remaining patients seem to suffer no re-occlusion as a result of the initial procedure. But the large percentage of patients who

do require re-treatment, and the additional cost and risk involved, belies the significance of a reported 95% success rate for the initial unblocking procedure. Where re-occlusion occurs, the patient is faced with the prospect of open heart surgery. Restenosis is actually attributable to an injury response mechanism of the tissue

to the unblocking procedure, rather than to a new buildup of plaque, at least for a substantial

percentage of the patients. Attempts to avoid the restenosis problem by use of drugs have not

been successful.

Irradiation of the vessel wall with a radioactive source appears to alleviate the

restenosis problem in findings from tests conducted on rabbits and rats. But to deliver the

radiation from within the vessel by means of a source wire imposes an even greater requirement of wire thinness, flexibility, and strength to enable the source to reach the target area, because

of the small size of the coronary arteries and the tortuous pathway that must be navigated through the vascular system. Adding to the problems is the fact that the patient is susceptible

to heart attack if a critical vessel is blocked for an inordinate time during performance of the

treatment. Thus, similar or even greater problems are encountered for coronary radiotherapy, compared to tumor treatment by brachytherapy.

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.

Treatment for heart attack victims incurs considerable cost, antithetical to

efforts toward cost containment by treatment centers and other care providers. On the other hand, treatment which is unsuccessful, inadequate or untimely bears an even greater cost — 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, such as that attributable to procedures

performed for opening occluded blood vessels.

Summary of the Invention

According to the present invention, there is provided a new and improved

radioactive source wire, and apparatus and methods of use thereof, which are equally suited

for brachytherapy and vascular radiotherapy applications. The source wire of the invention is

composed of a nickel-titanium alloy, known commercially as nitinol, which has desirable

properties of flexibility, springiness, slipperiness, mechanical strength and super-elasticity that give the wire a normally straightened shape when unstressed and the capability to undergo

significant deformation without permanent effect when stressed as by being advanced through

a narrow tortuous pathway for treatment, and to revert to the straightened shape after being withdrawn from the tortuous pathway. Radioactive source material, such as Ir-192 (iridium

isotope) spheres, may be loaded into an axial hole in the distal tip of the wire, which is then

sealed with a nitinol plug such as by welding. As a consequence of its desirable properties, the nitinol source wire is readily returned by the drive system of the afterloader to safe storage,

without likelihood of kinks or bends, for subsequent use in another or other procedures of the same type.

The wire is composed of a shape memory alloy, the nickel/titanium alloy known

as nitinol being preferred. Such material possesses 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.

Nitinol has been used commercially in bendable frames for lenses (eyeglasses). It has also been used in the past for guidewires (rails) 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 guidewire dispenses with the need to

relocate 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.

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 because of the large number of targets (i.e., plural tumor treatment sites which may be anywhere in the body, versus

targets at or in the region of the heart for the coronary machine), and consequent multiple channels (up to about 20) versus only one channel required for the coronary radiotherapy

machine. Thus, the coronary afterloader need not have a turret, or at most, a two-position

turret, whereas the turret of the brachytherapy afterloader has multiple positions corresponding to the number of channels available for delivery of treatment. The basic structure of each machine may be entirely conventional.

In the coronary radiotherapy treatment procedure of the invention, the

afterloader equipment is adapted to advance a simulation wire (non-radioactive) through the

implanted catheter until the distal tip of the wire is positioned at the target site by visual

observation such as fluoroscopy, after which the simulation wire is retracted. The source wire

is then automatically advanced through the catheter to position the source at the target site 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 simulation 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 simulation 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.

A treatment catheter is coupled to the end of the afterloader connector and

deployed over a guidewire to the target site for subsequent delivery and retraction of the

radioactive source on the source wire. In the case of coronary radiotherapy, the source

material in the source wire must be centered radially in the lumen of the coronary artery to the

maximum practicable extent, so as to provide uniform irradiation of tissue in a circumferential

band about the axis of the source wire viewed in a plane orthogonal to that axis through the

source, in the physician-prescribed dosage, to achieve beneficial results (i.e., inhibition of restenosis). A non-centered source would deliver too small a dose of radiation to one side of

the artery interior wall, resulting in lack of effective treatment of that region, and too large a dose of radiation to the other side of the artery interior wall, resulting in possible injury to

tissue in that region.

Summary of the Drawings

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:

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;

FIG. 2 is a fragmentary, perspective view of a catheter, guidewire, and source

wire connected at the proximal end to the afterloader drive connector;

FIG. 3 is a simplified side view of the system of FIG. 2;

FIG. 3 A is a sectional view through the lines A-A of FIG. 3;

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; FIG. 5 A is a plan view of a centering balloon according to the present invention;

and

FIG. 5B is a perspective view of the centering balloon of FIG. 5 A of a section taken through a plane containing the line 5-5.

Detailed Description of the Preferred Embodiment and Method

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 changes for the cardiac application.

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

afterioaders and treatment rooms would be provided for the two different applications. The

description 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.

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 level radioactivity treatment is being performed, but with the attendant (and console) shielded by a set of radiation screens 25. For high level radioactivity

treatments the console (and attendant) may be located outside the shielded treatment room.

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 posi¬

tioned to allow attendant 20 to view the patient, with equipment including display controls 31 positioned within easy access by the attendant.

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 radioactivity level requirements,

may be used for either procedure.

According to the preferred embodiment of the invention, the source wire is an assembly including an elongate wire composed of a nickel/titanium alloy commercially

marketed as nitinol. Nitinol itself is available, for example, from Shape Memory Alloys of Sunnyvale, California. The material is described, for example, in U.S. Patent No. 4,665,906.

For purposes of the source wire application according to the invention, the nickel-titanium alloy which gives the wire its super-elastic properties is stored in its austenitic state, characterized

by a straightened shape of the wire. And when the wire is flexed in use, the alloy enters a

stress-induced martensitic state, which is characterized by a capability to undergo bending

without suffering permanent plastic deformation, as it moves through a tortuous path in the

human body. When the wire is formed, it undergoes processing that may involve several

separate treatments at high temperature, which enables selection of a transition temperature of

the material at which it is in its austenitic state. In the source wire of the invention, the nitinol

is always used for treatment at a temperature above the transition temperature, which is typically 15° C ± 5° C, for example, and is normally in the austenitic state except when the wire

is in flexation, at which time it assumes the stress-induced martensitic state. This is the case for the nitinol wire when used in either the brachytherapy or coronary radiotherapy application,

where it is bent and flexed as it is advanced or withdrawn through a tortuous path in the human

body or even when it is simply residing in the tortuous path.

In the preferred form the nitinol wire reassumes its straightness in the austenitic

state after stress is removed, despite having undergone severe deformation in the stress-

induced martensitic state while in tortuous pathways during use in the body. That is, upon

removal from the environment in which stresses on the nitinol wire have caused it to be in the

martensitic state, it reverts to the austenitic state in which it undergoes self-straightening.

For retention of its desired properties such as high flexibility, springiness,

slipperiness and mechanical strength in the austenitic state, 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.

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. Three alternative processes were employed to produce nitinol wire for use in

source wire according to the invention. It was necessary to produce the wire in its final form (i.e., with predetermined dimensional characteristics including desired diameter and length) and

to provide it with a cavity in which radioactive source material would be retained. In practice,

an axial hole may be formed at the distal end of the wire to house the source material, and the

hole occupied by the source material is subsequently sealed to prevent particulate loss and

contamination.

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, although it may be kept below 0.021 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 inventors by the Raychem Corporation of Menlo Park, California.

A second process, also performed by Raychem Corporation, produced a similar form of wire but which constituted 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 distal tip. This

portion is selected to provide 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.

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, Georgia. In contrast to the

other processes, the EDM process tended to produce a hole wall of somewhat varying thick¬

ness. In any event, however, the EDM process served to produce a hole of desired diameter

and depth in the distal end of the wire, without need for further drawing.

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 for the cardiac application, and from that activity up to

about 10 curies, according to physician-prescribed dosage, for the brachytherapy application.

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.

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.

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 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.

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.

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. In the cardiac application, the catheter is also coupled to the afterloader

connector 50 by a guidewire 52 which extends to the target site. The catheter for that application may be provided with small channels to allow sufficient blood flow (perfusion)

therethrough. The catheter 12 is placed over the guidewire 52 which is hooked into the

connector for the afterloader as well. The afterloader connector 50 is also coupled to the

turret. Since the guidewire 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 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.

The cardiac application of the radioactive source wire is extremely size sensitive.

Among critical issues for that application are flexibility of the wire for passage through the fine

and tortuous pathways to the very fine and remote blood vessels, wire size for entry into the

vessels, and radial centering of the radioactive source in the lumen of the vessel.

A suitable level of radioactivity for the source in the cardiac application is one

curie, and such a source would be maintained centered in the lumen of the vessel for a time

interval sufficient to produce, say, 1,000 to 1,500 rads or other dose within a prescribed

therapeutic range of efficacy, at a one millimeter distance from source to the vessel 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. Without adequate perfusion, the patient can only tolerate one to one and a half minutes of total occlusion in the target area, which means that in some cases it may be

necessary to end treatment before the limit is reached. In that case, the attending personnel are

allowed to 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.

It is imperative to provide centering of the distal tip of the wire in the lumen of

the vessel. The concern for achieving centering is lessened for smaller diameter arteries

approaching the diameter of the source wire, but remains nevertheless. With an uncentered

distal tip, for example, one side of the interior surface of the artery may be 2Vι mm from the

source, while the other may be 2 mm from the source. This lack of centering will create a hot

spot (i.e., overexposure) on the closer side, and a cold spot (i.e., underexposure) on the further

side. Preliminary results indicate that failure to reach a certain threshold dose of radiation on

the vessel wall, about 1,000 rads, will result in no discernible prevention of restenosis.

In the preferred embodiment, an inflatable balloon 60 (FIG. 5 A) is provided in the catheter for centering the source tip of the source wire. A dose of 1,000 to 1,500 rads to

tissue at a given distance of the vessel wall from the source (actually, from the distal tip of the

source wire) requires a specified activity level for the source, which drops off according to the inverse square of the distance, and an appropriate period of treatment. The treatment catheter

may include, in addition to the working treatment (i.e., radiotherapy source wire) channel or lumen 54, a guidewire lumen 58, and a lumen 56 for inflating the centering balloon. Segmented

or fluted balloons, or otherwise channeled balloons may be used, alone or together with a

catheter, to permit adequate blood flow while the treatment is taking place with the balloon

inflated, and thereby avoid a need to withdraw the source wire before the treatment period is completed because of blockage.

In brief, the treatment method for a coronary artery is performed substantially

immediately after the artery has been subjected to a procedure for opening the lumen. The method includes 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. The elongate lead is selected to be sufficiently flexible and mechanically strong to

traverse the catheter without substantial kinking while resisting breakage. The advance of the

source wire through the catheter is halted when the distal end (i.e., the tip) reaches the point

at which the source wire is to irradiate tissue in the target area, the distal tip of the source wire is centered in the lumen of the coronary artery to produce substantially uniform irradiation of

the radioactive tissue in a circumferential region of the arterial tissue adjacent the source, as the targeted tissue is irradiated for a predetermined interval of time sufficient to deliver a prescribed dose of radiation. The source wire is withdrawn from the catheter immediately when the time

interval has elapsed.

A type of centering mechanism other than a balloon may be used, although the

centering balloon is preferred, but should also be of a type and shape that will permit sufficient

blood flow so that the procedure need not be stopped before the treatment regimen is

completed. A disadvantage of using a different mechanism from a balloon is that the means for

deployment must be safe and reliable. Balloon inflation and deflation in a catheter is in and of itself a conventional procedure with a proven record of safety.

The irradiation procedure is preferably performed very soon after the balloon

angioplasty (PTC A) or other procedure for removing blockage of the vessel lumen is

completed. The guidewire is left in place during the period of treatment because it allows a

rapid return to the target. Since the guidewire is tiny, at 0.014 inch, it does not seriously

impede blood flow. Initially, the guidewire is steered into the part of the heart being targeted, using a fluoroscope, so that it becomes the first component in and the last out.

The catheter is placed over the guidewire, and in available size ranges, is capable

of moving through vessels or ducts as small as two mm in diameter. 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.

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 withdrawn and the balloon is deflated and the patient's

heart is allowed to reoxygenate. The control console of the afterloader enables programming of the desired functions. For example, a one to one and one-half minute interval may be timed

by the afterloader, the procedure halted at that point, and the source wire then retracted into the shielded safe. The afterloader retains all necessary data such as the dose delivered during

treatment at a particular point, and the dose delivered during transit of the source to and from

the point at which the procedure is initiated, or transit dose.

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.

Claims

What is claimed is:

1. A radioactive source wire adapted to traverse a tortuous path within a

patient's body through an implanted catheter or a natural vessel, duct or chamber of the body for localized in vivo radiation treatment of selected tissue at a target site within the body, said

source wire comprising:

a thin elongate member composed of nickel-titanium alloy having super-elastic properties, said super-elastic properties being characterized by a stress-induced martensitic

state in which said alloy when flexed will undergo bending without permanent plastic deformation so that said member can be readily and rapidly advanced or withdrawn along said

tortuous path without kinking, and further characterized by a straightened austenitic state to

which said alloy will revert when the member is relaxed so that said member will undergo self- straightening when removed from said tortuous path; and

a radioactive source secured at the distal end of said member and having a predetermined activity level for delivering a prescribed dose of radiation to said selected tissue

at the target site when positioned at the target site for a predetermined time interval.

2. The radioactive source wire of claim 1, wherein:

said member is a single, solid lead.

3. The radioactive source wire of claim 2, wherein: said member is tapered at the distal end.

4. The radioactive source wire of claim 2, wherein:

said radioactive source is secured at the distal end of said member within an axial hole sealed at the tip thereof.

5. The radioactive source wire of claim 1, wherein: said member is a multi-strand lead.

6. The radioactive source wire of claim 5, wherein: said member is tapered at the distal end.

7. The radioactive source wire of claim 5, wherein:

said radioactive source is secured at the distal end of said member within a

capsule axially affixed to the tip thereof.

8. The radioactive source wire of claim 1, wherein:

the activity level of said radioactive source is sufficient to deliver a prescribed

dose exceeding 1000 rads to selected tissue radially displaced from the source by a predetermined distance, over said predetermined time interval.

9. The radioactive source wire of claim 1, wherein:

said member comprises a hollow tube, and a solid backbone wire in the tube,

at least one of the tube and the backbone wire being composed of said nickel-titanium alloy.

10. The radioactive source wire of claim 9, wherein:

said backbone wire is assembled in and runs substantially the entire length of the

tube except that the distal end of the backbone wire is displaced short of the distal end of the

tube to form an axial hole of predetermined depth sufficient to house the radioactive source

therein.

11. Apparatus for intravascular radiation therapy to inhibit stenosis along

a preselected length of the lumen of a blood vessel of a patient, by irradiating tissue in the

vessel wall along said preselected length with a radioactive source of predetermined activity

level for a predetermined interval of time to deliver a prescribed dose of radiation to said tissue

at a predetermined radial distance from said source, said apparatus comprising:

a thin elongate wire-like member having dimensions and flexibility suitable to

enable the member to be moved rapidly through curved luminal passages of the vascular system

of the patient without kinking, so as to position the distal end of said member quickly and selectively along said preselected length of lumen;

a radioactive source of said predetermined activity level affixed substantially

axially at the distal end of said member; drive means for moving said member from the proximal end thereof; and

means for maintaining the distal end of said member substantially centered

axially in the lumen of the blood vessel along said preselected length thereof, when desired to

deliver the prescribed dose of radiation to said tissue from the radioactive source.

12. The apparatus of claim 11, wherein said maintaining means comprises

an inflatable centering balloon located adjacent the distal end of said member in the vicinity of

the radioactive source.

13. The apparatus of claim 12, wherein said member is composed of a

nickel-titanium alloy having super-elastic properties characterized by a normally straight

austenitic state, and by a stress-induced martensitic state in which said alloy is readily flexed

without undergoing permanent plastic deformation, said martensitic state being assumed by the

alloy only when subjected to bending, as occurs when the member is advanced or withdrawn

through or otherwise resides in said curved luminal passages of the vascular system, whereby

said alloy reverts to the austenitic state to undergo self-straightening when relaxed, as occurs

when said member is removed from the curved luminal passages.

14. The apparatus of claim 13, further including drive means for advancing

said member from the proximal end thereof along the luminal passages of the vascular system,

for ceasing advancement of said member when the radioactive source is selectively positioned along said preselected length of lumen, and for withdrawing said member from the luminal

passages at the end of said predetermined interval of time following cessation of advancement.

15. A method of intravascular radiation therapy to inhibit stenosis along a

preselected length of the lumen of a blood vessel of a patient, by irradiating tissue in the vessel wall along said preselected length with a radioactive source of predetermined activity level for

a predetermined interval of time to deliver a prescribed dose of radiation to said tissue at a predetermined radial distance from said source, said method comprising the steps of:

providing a thin elongate wire having dimensions and flexibility suitable to

enable the wire to be moved rapidly through curved luminal passages of the vascular system of the patient without kinking, so as to position the distal end of said wire quickly and

selectively along said preselected length of lumen; and with a radioactive source of said predetermined activity level affixed substantially axially at the distal end of said wire; and advancing the wire through said luminal passages until the distal end of the wire

is positioned along the preselected length of lumen, and maintaining the distal end of the wire

substantially centered axially in the lumen of the blood vessel along said preselected length

thereof, when desired to deliver the prescribed dose of radiation to said tissue from the

radioactive source. 98/34681

16. The method of claim 15, wherein the step of maintaining comprises

inflating a centering balloon at a location adjacent the distal end of said wire in the vicinity of

the radioactive source thereof.

17. The method of claim 16, wherein said wire is composed of a nickel-

titanium alloy having super-elastic properties characterized by a normally straight austenitic

state, and by a stress-induced martensitic state in which said alloy is readily flexed without undergoing permanent plastic deformation, said martensitic state being assumed by the alloy

only when subjected to bending, as occurs when the wire is advanced or withdrawn through

or otherwise resides in said curved luminal passages of the vascular system, whereby said alloy

reverts to the austenitic state when relaxed to undergo self-straightening, as occurs when said wire is removed from the curved luminal passages.

18. The method of claim 17, further including the steps of advancing said

wire from the proximal end thereof along the luminal passages of the vascular system, ceasing

advancement of the wire when the radioactive source is selectively positioned along said

preselected length of lumen, and withdrawing the wire from the luminal passages at the end of

said predetermined interval of time following cessation of advancement of the wire.