Patent Abstract:
A catheter capable of irradiating blood vessel walls to inhibit restenosis after angioplasty. Catheters are capable of simultaneous irradiation, angioplasty, and in some devices, drug infusion. Preferred catheters include a helical perfusion balloon having strand windings spaced apart when inflated and defining a perfusion lumen within. A tubular sheath over the helical strands and distal shaft region is used in some embodiments and defines an outer wall for the perfusion lumen. A spiral, inter-strand space is defined between the sheath outer wall and the blood vessel inner wall, providing a confined volume for controlled delivery of drugs to the vessel wall in conjunction with irradiation. A device having a radiation wire, distally closed-end tube is provided. A device having a radiation wire open ended tube terminating proximally of the perfusion lumen is also provided.

Full Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of application Ser. No. 08/868,482 filed Jun. 3, 1997 U.S. Pat. No. 5,855,546, which is a continuation-in-part of U.S. patent application Ser. No. 08/812,248, filed Mar. 6, 1997, entitled PERFUSION BALLOON AND RADIOACTIVE WIRE DELIVERY SYSTEM, now U.S. Pat. No. 6,099,454; which is a continuation-in-part of U.S. patent application Ser. No. 08/782,471, filed Jan. 10, 1997, entitled INTRAVASCULAR RADIATION DELIVERY SYSTEM, now U.S. Pat. No. 6,234,951; which is a continuation-in-part of U.S. patent application Ser. No. 08/608,655, filed Feb. 29, 1996, now U.S. Pat. No. 5,882,290; the entire disclosures of which are herein incorporated by reference. This application is related to U.S. Pat. No. 5,558,642, entitled DRUG DELIVERY CATHETER, also incorporated by reference. 
    
    
     FIELD OF THE INVENTION 
     The present invention relates generally to intralumenal or intravascular catheters used to delivery radiation inside a living body. More specifically, the present invention relates to radioactive perfusion balloon catheters for therapeutic purposes. 
     BACKGROUND OF THE INVENTION 
     Intravascular diseases are commonly treated by relatively non-invasive techniques such as percutaneous transluminal angioplasty (PTA) and percutaneous transluminal coronary angioplasty (PTCA). These therapeutic techniques are well known in the art and typically involve use of a guide wire and a balloon catheter, possibly in combination with other intravascular devices. A typical balloon catheter has an elongate shaft with a balloon attached to its distal end and a manifold attached to the proximal end. In use, the balloon catheter is advanced over the guide wire such that the balloon is positioned adjacent a restriction in a diseased vessel. The balloon is then inflated and the restriction in the vessel is opened. 
     Vascular restrictions that have been dilated do not always remain open. In approximately 30% of the cases, a restriction reappears over a period of months. The mechanism of this restenosis is not understood. The mechanism is believed to be different from the mechanism that caused the original stenosis. It is believed that rapid proliferation of vascular smooth muscle cells surrounding the dilated region may be involved. Restenosis may be in part a healing response to the dilation, including the formation of scar tissue. 
     Drug infusion near the stenosis has been proposed as a means to inhibit restenosis. U.S. Pat. No. 5,558,642 to Schweich, Jr. et al. describes drug delivery devices and methods for delivering pharmacological agents to vessel walls in conjunction with angioplasty. 
     Intravascular radiation, including thermal, light and radioactive radiation, has been proposed as a means to prevent or reduce the effects of restenosis. For example, U.S. Pat. No. 4,799,479 to Spears suggests that heating a dilated restriction may prevent gradual restenosis at the dilation site. In addition, U.S. Pat. No. 5,417,653 to Sahota et al. suggests that delivering relatively low energy light, following dilatation of a stenosis, may inhibit restenosis. Furthermore, U.S. Pat. No. 5,199,939 to Dake et al. suggests that intravascular delivery of radioactive radiation may be used to prevent restenosis. While most clinical studies suggest that thermal radiation and light radiation are not significantly effective in reducing restenosis, some clinical studies have indicated that intravascular delivery of radioactive radiation is a promising solution to the restenosis enigma. 
     Since radiation prevents restenosis but will not dilate a stenosis, radiation is preferably administered during or after dilatation. European Pat. No. 0 688 580 to Verin discloses a device and method for simultaneously dilating a stenosis and delivering radioactive radiation. In particular, Verin discloses a balloon dilatation catheter having an open-ended lumen extending therethrough for the delivery of a radioactive guide wire. 
     One problem associated with the open-ended lumen design is that bodily fluids (e.g., blood) may come into contact with the radioactive guide wire. This may result in contamination of the guide wire bodily fluid and require the resterilization or disposal of the radioactive guide wire. To address these issues, U.S. Pat. No. 5,503,613 to Weinberger et al. proposes the use of a separate closed-ended lumen in a balloon catheter. The closed-ended lumen may be used to deliver a radioactive guide wire without the risk of contaminating the blood and without the need to resterilize or dispose of the radiation source. 
     The closed-ended lumen design also has draw backs. For example, the addition of a separate delivery lumen tends to increase the overall profile of the catheter. An increase in profile is not desirable because it may reduce flow rate of fluid injections into the guide catheter and it may interfere with navigation in small vessels. 
     Another problem with both the open-ended and closed-ended devices is that radiation must travel through the fluid filled balloon in order to reach the treatment site. While this is not a problem for gamma radiation, it poses a significant problem for beta radiation which does not penetrate as well as gamma radiation. Beta radiation is considered a good candidate for radiation treatment because it is easy to shield and control exposure. In larger vessels (e.g., 0.5 cm or larger), a fluid filled balloon absorbs a significant amount of beta radiation and severely limits exposure to the treatment site. 
     Other intravascular treatments, including delivery of radioactive radiation have been proposed as a means to prevent or reduce the effects of restenosis. Dake et al. suggest delivering radiation within the distal portion of a tubular catheter. Fischell, in the publication EPO 0 593 136 A1, suggests placing a thin wire having a radioactive tip near the site of vessel wall trauma for a limited time to prevent restenosis. Problems exist in attempting to provide uniform radiation exposure using a point or line source. Specifically, as the radiation varies inversely with the square of distance for a point source and inversely with distance for a line source laying off center near one vessel wall may significantly overexpose the nearby wall while underexposing the further away wall. This is especially critical for beta radiation which is absorbed by tissue and blood at a relatively short distance from the source. 
     Bradshaw, in PCT publication WO 94/25106, proposes using an inflatable balloon to center the radiation source wire tip. In PCT publication WO 96/14898, Bradshaw et al. propose use of centering balloons which allow blood perfusion around the balloon during treatment. U.S. Pat. No. 5,540,659 to Tierstein suggests use of a helical centering balloon, attached to a catheter at points about the radiation source to allow perfusion through the balloon, between the balloon and radiation ribbon source. 
     Use of continuous centering balloons, having a beta radiation source within, significantly attenuate the beta radiation when filled with inflation fluid and they may also allow the radiation source to “warp” when placed across curved vessel regions, allowing the balloon to bend but having the central radiation source lying in a straight line between the two ends. Segmented centering balloons may improve the warping problem but may have significant beta attenuation due to blood standing or flowing between the beta source and vessel walls. What remains to be provided is an improved apparatus and method for delivering uniform radiation to vessel interiors to inhibit restenosis. What remains to be provided is an improved perfusion catheter having radiation delivery and drug infusion capabilities. 
     SUMMARY OF THE INVENTION 
     The present invention includes devices and methods for providing radiation to the interior of human body vessels. Preferred devices include both devices having spaced apart, sparse helical windings and devices having tightly wound, closely spaced helical or spiral windings. Preferred sparsely wound devices include a helical perfusion balloon, having at least one helical strand configured into multiple windings having the windings spaced apart longitudinally. The preferred device includes a balloon assembly disposed at the distal region of a catheter shaft, where the catheter shaft includes an inflation lumen, a radiation wire lumen, and a drug infusion lumen. In the distal region, the radiation wire lumen can be disposed above the shaft, making room for a distal, single-operator-exchange guide wire lumen. The spiral, inflatable windings are laced inside shaft through-holes transverse to the shaft longitudinal axis and preferably off center. Lacing the helical strand through the shaft secures the helical balloon to the shaft. Lacing the strands also provides positions along the shaft in between windings for the placement of drug infusion apertures. Preferred devices include a tubular sheath over the helical balloon and shaft distal region, defining a perfusion lumen outer wall. The sheath preferably is snugly attached to both the exterior contours of the individual helical balloon strand windings and the catheter shaft. 
     One sparsely wound device includes a closed end radiation tube extending through a substantial portion of the balloon. This device allows for use and re-use of non-sterilized radiation sources with the sterile catheter. Another device includes an open ended radiation tube terminating distally near the proximal end of the balloon and not extending substantially through the balloon. This device allows extension of a radiation wire or source through the balloon, without having a radiation wire tube within the perfusion lumen within the balloon. The open ended radiation wire tube embodiment provides greater perfusion cross-sectional area due to the lack of the additional tube within the perfusion flow area. The open ended embodiment can also provide a smaller, uninflated profile. 
     In devices supporting drug infusion, drug infusion apertures extend through the catheter shaft distal region between balloon strand windings. The infused drug exits the apertures into the inter-strand spaces outside the tubular sheath and contacts the inside of the enclosing blood vessel wall. The drug can spread around the outside of the perfusion sheath through the spiral shaped spaces created by the helical strand windings underneath the tubular sheath material. The confined space allows concentrated drug delivery against the vessel wall. It is believed the combined radiation and drug delivery can significantly inhibit restenosis. 
     Preferred tightly wound or closely spaced helix devices include a helical, perfusion balloon, having at least one helical strand configured into multiple windings. The helical balloon adjacent windings are closely spaced or in contact when inflated so as to have insubstantial space separating them. The tight spiral windings or closely spaced windings improve centering of the catheter in the curved or tortuous vascular system due to many more balloon segments than lobed designs. The balloon is capable of being inflated with a gas. Using gas to inflate the balloon results in decreased absorption of radiation by the inflated balloon interior. The passage of beta radiation is especially improved by use of a gas rather than a liquid for inflation. Gas allows beta radiation to pass relatively unhindered from beta source to the balloon wall. 
     In a first closely spaced helix embodiment, the catheter device is a “single operator exchange” catheter suitable for use with a removable, preferably sheathed, radiation source. A second closely spaced helix embodiment includes an “over the wire” catheter suitable for use with a removable, preferably sheathed, elongate radiation source. Yet another closely spaced helix embodiment is a single operator exchange device having a combination use lumen partitioned into sterile and non-sterile portions by a permanent sheath extending within the catheter lumen. A guide wire can be inserted through the sterile portion, and a radiation source can be inserted through the non-sterile portion. Maintaining a non-sterile portion separate from contact with the patient allows for use of non-sterilized or non-sterilizable radiation sources, while abating the risk of infection for the patient. Radiation sources in the sterilized portion can be re-used without sterilization, saving considerable time and expense. 
     Single operator exchange devices according to the present invention can have a proximal, extended entry lumen. This allows for retracting a guide wire distal portion out of the lumen area used in common by both the guide wire and the radiation source. The extended entry lumen is sufficiently long to allow the guide wire to maintain position within the catheter, when lying within, yet does not interfere with insertion of the radiation source through the length of the catheter. 
     In use, the above mentioned devices can be used for irradiation only, drug infusion, or for concurrent irradiation, drug infusion, and angioplasty. The devices can be advanced over a guide wire, the guide wire retracted, the balloon inflated and the radiation source inserted. After angioplasty and/or irradiation and/or drug infusion are complete, the radiation source can be retracted, the guide wire advanced, and the catheter retracted over the guide wire while maintaining the wire across the treated area. 
     The present invention also provides a radiation delivery system that permits the use of an open-ended delivery lumen without the risk of blood contamination and without the need to dispose of or resterilize the radiation source. In addition, the present invention provides a radiation delivery system that permits beta radiation to be delivered through a balloon without a significant decrease in radiation exposure to the treatment site, even in large vessels. 
     One embodiment of the present invention may be described as a catheter having an open-ended lumen, a radiation source disposed in the open-ended lumen of the catheter and a closed-end sheath surrounding the radiation source. The closed-end sheath prevents blood or other fluids from coming into contact with the radiation source so that blood does not contaminate the radiation source and it may be reused. The catheter may be a balloon catheter and may include a guide wire disposed in the open-ended lumen of the catheter. The open-ended lumen may be a full-length lumen or a partial-length lumen (e.g., a rapid exchange lumen). Preferably, the lumen is centered in the balloon for uniform radiation delivery. The catheter may also include a blood perfusion lumen under the balloon or around the balloon. The open-ended lumen in the catheter may have a reduced diameter adjacent the distal end of the catheter to prevent the radiation source from exiting the lumen. Alternatively, the closed-end sheath may have a ridge which abuts a corresponding restriction in the open-end lumen of the catheter to prevent the radiation source from exiting the lumen. 
     Another embodiment of the present invention may be described as a method of delivering radiation to a treatment site inside the vasculature of a patient using the radiation delivery system described above wherein the method includes the steps of (1) inserting the catheter into the vasculature of a patient; (2) inserting the radiation source into the closed-end sheath; (3) inserting the radiation source and the closed-end sheath into the lumen of the catheter such that the radioactive portion is positioned adjacent a treatment site; and (4) exposing the vascular wall to radiation from the radiation source. Alternatively, the sheath may be inserted into the catheter before the radiation source is loaded into the sheath. The method may also include the steps of (5) removing the radiation source from the catheter; and (6) removing the catheter from the patient. The catheter may be inserted into the vasculature over a guide wire and the guide wire may be removed from the catheter prior to exposing the vascular wall to radiation. 
     Yet another embodiment of the present invention may be described as a method of delivering radiation to a treatment site inside the vasculature of a patient using a gas-filled balloon catheter and a radiation source wherein the method includes the steps of: (1) inserting the catheter into the vasculature such that the balloon is adjacent to a treatment site; (2) inflating the balloon with a liquid or gas; (3) inserting the radiation source into the catheter such that the radioactive portion is adjacent to the balloon; and (4) exposing the treatment site to radiation from the radiation source through the gas in the balloon. The balloon may be inflated prior to or subsequent to inserting the radiation source. Preferably beta radiation is used, but other radioisotopes may be employed. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a partially sectioned side view of an embodiment of the present invention; 
     FIG. 2 is a cross-sectional view taken at A—A in FIG. 1; 
     FIG. 3 is a side view of an alternative embodiment of the present invention including a helical-shaped balloon; 
     FIG. 4 is a side view of an alternative embodiment of the present invention including a toroidal-serpentine-shaped balloon; 
     FIGS. 5 a,    5   b  and  5   c  are partially sectioned side views of an alternative embodiment of the present invention including a rapid-exchange guide wire lumen; 
     FIG. 6 is a partially sectioned side view of an alternative embodiment of the present invention including a perfusion lumen passing through the balloon; 
     FIG. 7 is a cross-sectional view taken at B—B in FIG. 6; 
     FIG. 8 is a cross-sectioned side view of an alternative sheath of the present invention; 
     FIG. 9 is a lengthwise, longitudinal cross-sectional view of an single operator exchange catheter according to the present invention; 
     FIG. 10 is an enlarged, lengthwise longitudinal cross-sectional view of a distal portion of the catheter of FIG. 9; 
     FIG. 11 is a lengthwise, longitudinal cross-sectional view of an over-the-wire catheter according to the present invention; 
     FIG. 12 is a lengthwise, longitudinal cross-sectional view of a single operator exchange catheter having a sheath according to the present invention; 
     FIG. 13 is a lengthwise, longitudinal cross-sectional view of the catheter of FIG. 12 having a guide wire inserted past the sheath; 
     FIG. 14 is a cross-sectional view of the catheter of FIG. 13 taken through  14 — 14 ; 
     FIG. 15 is a fragmentary, side view of a sparsely wound balloon on a radiation delivery catheter; 
     FIG. 16 is a fragmentary, side view of the distal region of the catheter of FIG. 15; 
     FIG. 17 is a cross-sectional view taken through line  17 — 17  in FIG. 15, illustrating a proximal catheter shaft cross-section; 
     FIG. 18 is a cross-sectional view taken through line  18 — 18  in FIG. 16, illustrating a distal catheter shaft cross-section; 
     FIG. 19 is a cross-sectional view taken through line  19 — 19  in FIG. 16, projected through one complete inflation coil revolution; 
     FIG. 20 is a cross-sectional view taken through line  20 — 20  in FIG. 16, shown without the inflation coil, illustrating infusion openings; 
     FIG. 21 is an enlarged fragmentary bottom view taken through line  21 — 21  in FIG. 16, illustrating an inflation coil laced through holes in the catheter shaft; 
     FIG. 22 is a fragmentary side view of a radiation wire member including a tube with radioactive coil; and 
     FIG. 23 is a fragmentary, side view of a catheter distal region having a radiation wire tube terminating proximate the proximal end of the inflation coil. 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     Refer now to FIGS. 1 and 2 which illustrate one embodiment of a radiation delivery system  10  of the present invention. Radiation delivery system  10  includes a catheter  11  having an open-ended lumen  12  extending therethrough. A closed-ended sheath  13  surrounds a radiation source  14  (such as a guide wire) disposed in the open-ended lumen  12 . An after-loader  22  may be connected to the proximal end of the radiation source  14  to advance and retract the radiation source  14  and safely contain it when not in use. 
     The catheter  11  includes an inflatable balloon  15  having an interior  16  which is in fluid communication with an inflation lumen  17 . The catheter  11  illustrated in FIGS. 1 and 2 has a coaxial shaft construction including an inner tube  23  and an outer tube  24 . Other shaft constructions may be employed such as a dual lumen shaft design illustrated in FIG. 6. A manifold  18  is connected to the proximal end of the catheter  11  and includes a guide wire port  19  and a flush port  20  both of which are in fluid communication with the open-ended lumen  12 . The guide wire port may include a toughy-borst (not shown) to seal about the proximal end of the closed-end sheath  13 . The manifold  18  also includes an inflation port  21  which is in fluid communication with the inflation lumen  17  and the interior  16  of the balloon  15 . 
     The closed-end sheath  13  preferably extends to the proximal end of the catheter  11  and may include means for connection to the after-loader  22 . The closed-end sheath  13  may be formed of polyethylene, PTFE coated polyimide or other suitable flexible material. The closed-end sheath  13  may have a length of about 100 to 300 cm depending on the length of the catheter  11 . A wall thickness between 0.0002 and 0.005 inches is preferred to minimize profile and radiation absorption. 
     As included with catheter  11  illustrated in FIGS. 1 and 2, the open-ended lumen  12 , closed-ended sheath  13 , radiation source  14 , after loader  22  and toughy-borst are also included with catheters  31 ,  41 ,  51  and  61  as illustrated in FIGS. 3,  4 ,  5  and  6 , respectively. In addition, those skilled in the art will appreciate that the various features of each catheter  11 ,  31 ,  41 ,  51  and  61  may be mixed and matched depending on the desired result. For example, the rapid exchange features of catheter  51  may be incorporated into perfusion catheter  61 , resulting in a perfusion rapid exchange catheter for the delivery of radiation. As another example, the centering balloon  35  or  45  may be contained inside balloon  15  of catheters  11  and  61  to provide a centering function, even in curved vasculature. 
     Refer now to FIGS. 3 and 4 which illustrate alternative radiation delivery catheters  31  and  41 . Alternative catheters  31  and  41  may be used in place of catheter  11  for the radiation delivery system  10  illustrated in FIG.  1 . Except as described herein, the design and use of alternative catheters  31  and  41  is the same as catheter  11 . Alternative catheter  41  may be made as described in co-pending U.S. patent application Ser. No. 08/608,655 which is incorporated herein by reference. Similarly, alternative catheter  31  may be made as described in the above-referenced case except that the balloon  35  is wound in a helical shape rather than a serpentine shape. 
     With reference to FIG. 3, alternative catheter  31  includes a helically-shaped balloon  35  which is wound around the distal end of the catheter  31 . When the helically-shaped balloon  35  is inflated, a helically-shaped perfusion path  36  is defined between the balloon  35 , the shaft  37  and the inside surface of the blood vessel. The blood perfusion path  36  allows blood to flow across the treatment site while the balloon  35  is inflated. In addition, the concentric and flexible helical shape of the inflated balloon  35  maintains the distal portion of the catheter  31  centered in the vessel, even around turns in the vasculature. Having the catheter  31  centered in a vessel permits the uniform distribution of radiation to the treatment site. 
     The distal end of the shaft  37  may include a reduced diameter tip  38  with a corresponding reduced inside diameter open-ended lumen (not visible). The reduced inside diameter permits a conventional guide wire to exit out the distal end of the catheter  31  but prohibits the sheath  13  and radioactive source wire  14  from exiting. This assumes, of course, that the sheath  13  or radioactive source wire  14  is larger than the guide wire. A reduced diameter tip may be included on any of the catheters described herein. 
     With reference to FIG. 4, alternative catheter  41  includes a toroidal-serpentine-shaped balloon  45 . When the serpentine-shaped balloon  45  is inflated, a linear perfusion path  44  is defined between the balloon  45 , the shaft  47  and the inside surface of the blood vessel. The blood perfusion path  44  allows blood to flow across the treatment site while the balloon  45  is inflated. As with the helical balloon described above, the concentric and flexible serpentine shape of the inflated balloon  45  maintains the distal portion of the catheter  41  centered in the vessel, even around turns in the vasculature. Having the catheter  41  centered in a vessel permits the uniform distribution of radiation to the treatment site. A further advantage of the serpentine-shaped balloon  45  is the relative linearity of the perfusion path  44  which tends to minimize resistance to blood flow. 
     Catheter  41  may also include two radiopaque markers  46  to facilitate radiographic placement in the vasculature. The distal end of the shaft  47  may include a reduced diameter tip  48  with a corresponding reduced inside diameter open-ended lumen (not visible). The reduced inside diameter permits a conventional guide wire to exit out the distal end of the catheter  41  but prohibits the sheath  13  and radioactive source wire  14  from exiting. 
     It is also contemplated that both the helical balloon  35  and the serpentine balloon  45  may be covered with an elastomeric sleeve to aid in collapsing the balloon  35 / 45  upon deflation. This sleeve would be connected to the shaft adjacent the proximal and distal ends of the balloon  35 / 45 . It is further contemplated that this sleeve may include perfusion holes both proximally and distally to permit blood perfusion along the perfusion path  36 / 44  defined by the balloon  35 / 45 . If a gas is used to inflate the balloon  35 / 45  in large diameter vessels (e.g., peripheral vasculature), it is preferred to not permit perfusion of blood which would otherwise absorb beta radiation. In such a situation, the sleeve would not include perfusion holes. 
     Refer now to FIGS. 5 a,    5   b  and  5   c  which illustrate a rapid-exchange embodiment of the present invention. Alternative catheter  51  may be used in place of catheter  11  for the radiation delivery system  10  illustrated in FIG.  1 . Except as described herein, the design and use of alternative catheter  51  is the same as catheter  11 . 
     Rapid-exchange catheter  51  includes an elongate shaft  57  with a manifold  52  connected to the proximal end and a balloon  45  connected to the distal end. Although catheter  51  is shown with a serpentine balloon  45  and a corresponding linear perfusion path  44 , any of the balloon types described herein may be used. 
     The manifold  52  includes a balloon inflation port  53  which is in fluid communication with the balloon  45  via a conventional inflation lumen. A radiation source entry port  54  is also included in the manifold  52 . The entry port  54  communicates with the open-ended lumen and permits the insertion of the sheath  13  and radiation source  14 . The open-ended lumen terminates in a reduced diameter tip  58  which permits a conventional guide wire  56  to exit out the distal end of the catheter  51  but prohibits the sheath  13  and radioactive source wire  14  from exiting. 
     The guide wire  56  enters the shaft  57  at the proximal guide wire tube  55 . The guide wire tube  55  is located near the distal end of the catheter to permit catheter exchange without the need for an extension wire or wire trapping device. As best seen in FIG. 5 c,  the guide wire tube  55  has sufficient length such that the guide wire  56  may be pulled back and out of the open-ended lumen. In particular, the distance from the proximal end of the guide wire tube  55  to the distal end of the catheter  51  is less than the length of the guide wire extending outside of the patient&#39;s body. With the guide wire pulled back, the radioactive source wire  14  and the sheath  13  may be inserted into the entry port  54  to the distal end of the catheter  51 . 
     Refer now to FIGS. 6 and 7 which illustrate an alternative perfusion catheter  61 . Alternative catheter  61  may be used in place of catheter  11  for the radiation delivery system  10  illustrated in FIG.  1 . Except as described herein, the design and use of alternative catheter  61  is the same as catheter  11 . 
     Perfusion catheter  61  includes an elongate shaft  67  with a manifold  18  connected to the proximal end and a balloon  16  connected to the distal end. The shaft  67  is a multi-lumen type extrusion including an open-ended lumen  62  and an inflation lumen  63 . Inflation lumen  63  provides fluid communication between the inflation port  21  and the interior of the balloon  16 . Open ended lumen  62  is in communication with entry port  19  for the insertion of a guide wire (not shown) or the radioactive source  14  and sheath  13 . A guide wire extension tube  64  is connected to the distal end of the multi-lumen shaft  67  and rigidly connects to the distal end of the balloon  15 . 
     Catheter  61  includes a series of perfusion ports  65  which are in fluid communication with the distal portion of the open-ended lumen  62 . The perfusion ports  65  permit blood to flow across the treatment site via the open-ended lumen while the balloon  15  is inflated. 
     With reference now to FIG. 8, an alternative sheath  81  is illustrated. Alternative sheath  81  may be used in place of sheath  13  for the radiation delivery system  10  illustrated in FIG.  1 . Except as described herein, the design and use of alternative sheath  81  is the same as sheath  13 . 
     Sheath  81  includes a proximal portion  82  and a distal portion  83 , wherein the proximal portion  82  includes a relatively thicker wall and larger outside diameter. The thicker wall tends to absorb radiation to reduce the amount of unwanted exposure, particularly exposure of the medical personnel. The larger outside diameter of the proximal portion  84  may be used in conjunction with a corresponding restriction in the open-ended lumen  12  of any of the catheters described herein. Specifically, the leading edge or ridge  86  of the proximal portion  82  may abut a mating restriction in the open-ended lumen  12  such that the sheath  81  cannot be advanced beyond that point. The leading edge  86  and the mating restriction in the open-ended lumen serve the same function as the reduced diameter tip described previously and may be used in lieu thereof. In other words, the leading edge  86  and the mating restriction in the open-ended lumen would permit a conventional guide wire  56  to exit out the distal end of the catheter but would prohibit the sheath  81  and radioactive source wire  14  from exiting the distal end of the catheter. 
     The closed-end sheath  81  may include means for connection to the after-loader  22 . The closed-end sheath  81  may be formed of polyethylene, PTFE coated polyimide or other suitable flexible material. The closed-end sheath  81  may have a length of about 100 to 300 cm depending on the length of the catheter  11 . On the distal portion  83 , a wall thickness between 0.0002 and 0.005 inches is preferred to minimize profile and radiation absorption. On the proximal portion  82 , a wall thickness between 0.040 and 1.0 inches is preferred to maximize radiation absorption without significantly compromising profile. The outside diameter of the proximal portion  82  may be greater than the vascular access size on the portion of the sheath  81  that remains outside the body. Once the radiation source is inside the body, the risk of exposure of beta radiation to medical personnel is diminished. 
     Sheath  81  may also include a radiopaque marker  84  to facilitate radiographic placement of the sheath  81  and radioactive wire  14 . Such a radiopaque marker  84  may also be included on sheath  13 . 
     Sheath  81  may also include a series of annular magnets  85 . Magnets  85  may be used to interact with a series of magnets connected to the catheter  11 ,  31 ,  41 ,  51  or  61  or a series of magnets connected to a guide catheter (not shown). This general arrangement is described in more detail in PCT publication WO 95/21566 which is fully incorporated herein by reference. The interacting magnets provide a means to longitudinally control and stabilize the position of the radiation source relative to the patient and treatment site. 
     In practice, catheters  11 ,  31 ,  41 ,  51  and  61  may be used to delivery radiation to the vascular wall in the following manner. After vascular access is established and a guide catheter is in position (if desired), the catheter  11 / 31 / 41 / 51 / 61  is inserted into the patient with the distal portion adjacent the treatment site. If a guide wire is used, the guide wire may be inserted prior to or simultaneously with the catheter. The balloon is then inflated to a low pressure sufficient to center the balloon in the vasculature and prevent movement of the catheter relative to the treatment site. Optionally, the balloon may first be inflated to a higher pressure in order to dilate the treatment site. If desired, the balloon may be inflated with a gas such as nitrogen, carbon dioxide or other non-toxic gas to minimize the absorption of radiation by the inflation media. After dilatation, the balloon is maintained in an inflated state, preferably at a low pressure, to center the catheter in the vascular lumen. The sheath  13  is placed over the radiation wire  14 , preferably ahead of time, and the two are advanced into the open-ended lumen using an after-loader system. Optionally, the sheath  13  is first loaded into the open-ended lumen of the catheter and the proximal end of the sheath is connected to the after-loader, followed by insertion of the radioactive source wire  14 . The toughy-borst is maintained sufficiently loose to allow advancement and may be locked to fully seal about the sheath  13  once the radiation wire  14  and sheath  13  are in the desired position. If a guide wire is used in the open-ended lumen, the guide wire is preferably retracted to permit passage of the radioactive wire  14  and sheath  13 . If a rapid exchange catheter  51  is used, the guide wire is pulled back into the proximal guide wire tube  55 . The vascular wall is then exposed to radiation (preferably beta radiation) for the desired period of time. The radioactive wire  14  and sheath  13  are removed from the catheter  11 / 31 / 41 / 51 / 61  and the catheter is removed from the patient. 
     FIG. 9 illustrates a catheter  120  suitable for single operator exchange according to the present invention. Catheter  120  is illustrated attached to a manifold  122 , extending from a proximal portion  126 , to a distal portion  128 , to a distal end  130 . An elongate catheter shaft  123  includes a proximal outer tube  158 , an inner tube  154 , an intermediate outer tube  156 , and a necked inner tube  162 . A perfusion head  136  is located near catheter distal portion  128 . Perfusion head  136  includes a balloon  140  disposed about a perfusion tube  166  which defines a perfusion lumen  164 . Perfusion lumen  164  can transport blood from proximal perfusion ports  138  through to distal perfusion ports  132 . A proximal guide wire port  146  and extended entry guide wire lumen  148  allow insertion of a guide wire (not shown) through the catheter and out distal port  134 . 
     Referring now to FIG. 10, an enlarged view of a proximal portion of catheter  120  is illustrated. Balloon  140  as illustrated, includes a single strand  142  formed into a series of helical windings  144  about perfusion lumen  164 . Windings  144  are closely adjacent (preferably in contact when inflated) to each other, having little or no inter-strand spacing, as indicated at  145 . An inflation lumen  150 , extending proximally from balloon  140 , is in fluid communication with the interior of balloon  140 , indicated at  141 . Helical balloon  140  serves to center perfusion lumen  164 , and anything contained within, useful when the balloon is inflated in vessel curves or bends. 
     In use, a guide wire can be inserted within the vasculature of a patient and advanced to a stenosed site to be treated. Catheter  120  can then have the guide wire proximal end inserted through distal port  134 , through the balloon portion, through extended entry lumen  148 , and proximally out proximal guide wire port  146 . With the guide wire thus threaded, catheter perfusion head  136  can be advanced to the site to be treated. Once in position, a gas under pressure can be used to inflate balloon  140 . Either before, during, or after balloon inflation, the guide wire can be partially retracted such that the guide wire distal end is generally near the distal end of extended entry lumen  148 , indicated at  149 . The length of extended entry lumen  148  is such that the guide wire is able to maintain its position within the extended entry lumen without falling out. The guide wire should not extend distally so far that it interferes with advancement of a radioactive source, discussed below. 
     With the guide wire thus in position, a radioactive source can be advanced from catheter proximal portion  126  through shaft  123  past the distal end of inner tube  154 , indicated at  149 . A preferred radiation source is a beta emitter, but other radiation sources are contemplated and are within the scope of the invention. One preferred source is Nickel-66. The radioactive source can be advanced further, within perfusion lumen  164  within balloon  140 . The radioactive source outside diameter is small enough, and perfusion lumen inside diameter large enough, that sufficient blood is able to perfuse around the radioactive source and through perfusion lumen  164 . 
     With the radiation source thus disposed, the radiation is able to pass relatively unhindered through the gas filled interior  141  of balloon  140  to the surrounding vessel walls. In one method, the pressure is such that concurrent angioplasty and irradiation are carried out. In another method, only irradiation is performed, requiring lower gas pressure. In either of the aforementioned two methods, pressure is supplied sufficient to bring balloon  140  into close contact with the surrounding vessel walls. This excludes substantially all of the blood and external perfusing blood flow from between the balloon exterior and the vessel walls. This removal of interposing blood removes a source of beta radiation attenuation. 
     Once the radiation exposure period is complete, the radiation source can be withdrawn, and the guide wire can be advanced distally once more. In a preferred method, the radiation source is enclosed in a sheath. This allows for use of a non-sterile radiation source. This allows for use and re-use of a radiation source without requiring either sterilization or disposal of the radiation source. Sterilization or disposal is normally required after use, as the elongate radiation source has been in contact with the patients blood. This contact contaminates the exposed radiation source, requiring either disposal or subsequent sterilization. The sheath can be deployed within the catheter prior to radiation source advancement or slid over the radiation source outside of the catheter, and the sheathed source inserted into the catheter as a unit. 
     Referring now to FIG. 11, an “over-the-wire” embodiment of the present invention is illustrated. Catheter  121  is similar in many respects to catheter  120  of FIG. 9, but having an outer tube  157  having no proximal guide wire port suitable for “single operator exchange”. Rather, catheter  121  is suitable for use over a guide wire, where the guide wire extends from proximal portion  126  through distal portion  128  and out distal port  134 . 
     In use, a guide wire is positioned near a site to be treated. Catheter  121  can then be advanced over the guide wire, positioning perfusion head  136  near the treatment site. Inflation gas can them be supplied via inflation lumen  150 , inflating balloon  140  against the vessel walls. The guide wire can be withdrawn proximally out of the catheter, either before or after balloon inflation. A radioactive source, preferably in a sheath, can then be advanced distally through the catheter, advancement stopping when the radioactive source distal region is disposed within balloon  140 . 
     With the radioactive source disposed within the balloon, radiation treatment can continue for the appropriate time. The advantages of using a sheath, a gas filled balloon, and a tight, helical balloon are described above with respect to the embodiment of FIG.  9 . Once treatment is complete, the radiation source can be withdrawn. 
     Referring now to FIG. 12, a “single operator exchange” catheter  220  having a fixed sheath is illustrated. Catheter  220  is similar in many respects to catheter  120  of FIG. 9, with some similar reference numerals omitted for clarity. Catheter  220  includes a sheath  250  within shaft  123 , sheath  250  having a proximal portion  252  and a distal portion  254 , and is preferably fixed within shaft  123 , using a method such as adhesive bonding. A guide wire  222  is illustrated inserted into guide wire proximal entry port  146 , lying within extended entry lumen  148 . Guide wire  222  has a distal end  226 , indicating inserted as far as  224  in FIG.  12 . 
     FIG. 13 illustrates catheter  220  of FIG. 12 having guide wire  222  inserted distally past distal port  134 , to necked inner  162 . In this configuration, catheter  220  can be advanced or retracted over guide wire  222 . Sheath  250  is partially displaced radially by the insertion of the guide wire and does not interfere with guide wire insertion. FIG.  14  illustrates a cross section of catheter  220  taken through  14 — 14  in FIG. 13, showing that flexible sheath  250  is partially displaced by guide wire  222  being inserted through catheter  220 . Both sheath  250  and guide wire  222  are shown within necked inner tube  162 . The displacement of sheath  250  is indicated also at  255  in FIG.  13 . With guide wire  222  this far inserted, in preferred embodiments, there is insufficient room for insertion of an elongate radioactive source through to perfusion head  136 . 
     Catheter  220  is used in a similar manner to catheter  120  of FIG.  9 . Sheath  250  however is displaced by guide wire  222  during catheter advancement and retraction, when the radiation source is withdrawn sufficiently proximally so as to not interfere with guide wire movement within the catheter. Sheath  250  is at least partially filled by an elongate radiation source during radiation exposure of the vessel site. When sheath  250  is containing a radiation source, guide wire  222  is withdrawn sufficiently proximally so as to not interfere with radiation source placement yet lying sufficiently within the extended entry lumen  146  so as maintain guide wire position within the catheter. 
     Sheath  252  is an illustration of one aspect of the invention, the partitioning of a lumen into sterile and non-sterile portions. In FIG. 12, sheath lumen  252  does not have to be sterile, since it is not in contact with blood. Shaft lumen  125  external to sheath  252  is sterile to prevent patient exposure to infection. This partitioning, accomplished with a flexible partitioning means, allows dual, though not necessarily simultaneous, uses of a lumen. The distal portion of the lumen can be occupied by a disposable guide wire in the sterile portion during catheter advancement or retraction. The distal portion of the lumen can be occupied by a reusable, not necessarily sterile or sterilizable, radiation source once the catheter is in place. The catheter perfusion head  36  profile can thus be kept small by allowing sufficient lumen space for only the guide wire or the radiation source at one time, not both. 
     Totally enclosing the radiation source in a sheath illustrates one embodiment of the invention. In another embodiment, the lumen is partitioned into sterile and non-sterile portions by dividing the lumen along a longitudinal axis with a flexible wall or membrane, the wall extending across an intermediate portion of the lumen. In this later embodiment, the sterile portion of the lumen is formed in part by a flexible wall and in part by the usually more rigid lumen walls. Furthermore, in one embodiment, this flexible wall need extend longitudinally only from near the guide wire proximal entry port to near the lumen distal end. The remaining proximal portion of the lumen need not be divided by the wall in a single operator exchange embodiment, where there is no need to insert a guide wire. 
     FIG. 15 illustrates a sparsely wound radiation delivery catheter  320  including a tubular shaft  322  having a proximal region  324  and a distal region  326 , a manifold  328  disposed near shaft proximal region  324 , a balloon assembly  336  disposed on shaft distal region  326 , and a distal tip  338 . Shaft  322  includes a proximal shaft portion  352  and a distal shaft portion  354  and is preferably formed of polyethylene. Manifold  328  includes a radiation wire port  330 , an inflation port  332 , and an infusion port  334 . Radiation port  330  is used to insert an elongate radiation emitting member. Inflation port  332  is used to admit an inflation fluid to balloon assembly  336 . Infusion port  334  can be used to infuse drugs through to balloon assembly  336 . The present invention can be made in accordance with the drug delivery catheters described in U.S. Pat. No. 5,558,642, herein incorporated by reference. 
     In one embodiment, a catheter according to the present invention includes inflation and radiation wire lumens, but no infusion lumen. FIG. 15 illustrates a preferred embodiment catheter  320  having an infusion lumen as well. The inflation, radiation, and infusion lumens in preferred embodiments extend through shaft  322  to balloon assembly  336 . A preferred embodiment includes a distal, single-operator-exchange guide wire lumen having a proximal port  342  and a distal port  344 . 
     Referring now to FIGS. 16,  19  and  20 , FIG. 16 illustrates detail area  16  of FIG. 15, showing balloon assembly  336  in more detail in an inflated state. A radiation wire tube  358  defines a radiation wire lumen  360 , rising near radiation tube region  362  near proximal guide wire port  342  to accommodate entering guide wire tube  341  below, extending through a substantial portion of balloon assembly  336 , and ending in a radiation wire tube distal closed end  364 . Closed end  364  prevents fluid communication between bodily fluids and radiation wire lumen  360 , allowing use and re-use of radiation sources within the closed lumen without sterilization. The closed lumen allows use of non-sterile sources within a sterile catheter, as the radiation source does not contact the blood stream and become contaminated. In a preferred embodiment, the radiation wire tube lies external to the catheter shaft within the balloon assembly, as illustrated by radiation wire tube distal portion  358  lying atop shaft distal portion  354  in FIGS. 16,  19  and  20 . Radiation wire tube  358  can be formed of polyimide or PTFE. In a preferred embodiment, radiation wire tube  358  includes a distal segment formed of a collapsible polyolefin copolymer (POC) material within balloon assembly  336 , enabling increased perfusion when not occupied by a radiation wire. 
     Guide wire tube  341  extends from proximal entry port  342  through distal guide wire port  344 . Guide wire tube  341  is preferably formed of polyethylene. In a preferred embodiment, guide wire lumen  340  lies within shaft distal portion  354 . In catheter  320 , an infusion lumen  366  is defined between the outside walls of guide wire tube  341  and the inside walls of shafts  354  and  352 , as illustrated by FIGS. 17,  18 ,  19  and  20 . 
     In the embodiment shown, a helical balloon is formed of at least one inflatable helical strand or coil  346  having multiple windings extends longitudinally over a substantial portion of balloon assembly  336 . Balloon strand  346  is preferably formed of polyolefin. Balloon strand  346  is in fluid communication with an inflation lumen  349  within an inflation tube  348  and preferably has a blind, distal termination  396 . Inflation lumen  349  preferably lies within shafts  352  and  354 , as illustrated by inflation tube  348  lying within shafts  352  and  354 . Inflation tube  348  is preferably formed of polyimide. Balloon strand  346  can be attached to inflation tube  348  as illustrated at  350 . Balloon inflatable strand  346 , in an inflated state, defines a perfusion lumen  356  therethrough, as indicated in FIGS. 16,  19  and  20 . Perfusion lumen  356  does not lie uniformly around shaft  354  in a preferred embodiment, but has shaft  354  lying to one side of the lumen and forming a boundary of the lumen, as shown in FIG.  19 . 
     FIG. 19, illustrating a section taken through a complete inflation coil strand, shows the perfusion lumen created by the inflation of coil  346 . Perfusion lumen  356  allows perfusing blood flow during radiation treatment. As illustrated by FIGS. 19,  20  and  21 , distal shaft  354  has helix strand  346  secured by the lacing of strand  346  through through-holes  370 . FIG. 21 illustrates in detail the securing of balloon strand  346  to shaft  354  using holes  370 . In the embodiment shown, holes  70  form a pair aligned substantially transversely to the longitudinal axis of the shaft. In another embodiment, the through-holes can be oriented obliquely to the shaft longitudinal axis, substantially aligned with the helix strands as they approach the shaft. This later embodiment may not be self-securing and may require adhesive bonding to the shaft. 
     Lacing strand  346  repeatedly through shaft  354  removes shaft  354  to one side of perfusion lumen  356 , creating a greater unobstructed area for perfusing blood flow, compared to placing shaft  354  within the center. Placing shaft  354  to one side by threading strand  346  through pairs of holes in the shaft brings an exterior portion of the shaft into fluid communication with the space between strands  346 . As illustrated in FIG. 20, infusion holes  372 , preferably located between strands  346 , provide access from within infusion lumen  366  to the vessel wall the catheter is disposed within. 
     Infusion holes  372  and infusion lumen  366  can be used to infuse local agents in conjunction with radiation treatment. Infused substances can include agents to promote healing and agents to enhance the effect of radiation treatment. In particular, agents may be infused to prevent hypoxia (oxygen deprivation) while the balloon is inflated against vessel walls. Oxygenating agents include the patient&#39;s own arterial blood, which may be heparinized, and water or saline, which may be heparinized. Oxygenated blood, saline, water or other fluids can be used. Peroxides such as hydrogen peroxide can also be used to provide oxygen to vessel walls. Applicants believe the agents enhance the effectiveness of the radiation treatment. 
     Catheter  320  can also have a tubular sheath  374  disposed over strand  346  as illustrated in FIGS. 16 and 19. Sheath  374  is preferably formed of polyurethane elastomer. Sheath  374  is preferably configured to hug the contours of strand  346  such that inter-strand pockets  368  lie between the strands and also spiral around balloon assembly  336  as does strand  346 . If sheath  374  lay straight between the outermost extent of strands  346 , a substantially straight-walled cylindrical sheath would result, leaving less space between sheath and vessel wall for infusing drugs. As sheath  374  has inter-strand pockets  376 , there is space for drugs to circulate and diffuse to contact the vessel walls. While a helical coil without a sheath provides some reduced flow, dead space for drug infusion near vessel walls, a sheath substantially insulates the vessel walls from perfusion flow and is the preferred embodiment. 
     Referring now to FIG. 22, a radiation wire device  378  having a distal region  380  is illustrated. A radioactive coil  382  is preferably wound about a radiation wire support tube  384  having a lumen  386 . Support tube  384  is preferably formed of polyimide, having radioactive wire  382  wound around distal region  380  and covered with a shrink wrap layer  388  preferably formed of polyolefin copolymer. 
     In one embodiment, radiation wire support tube  384  is extremely flexible or floppy and incapable of being pushed alone through radiation wire lumen  360  from the catheter proximal end. In this embodiment, a radiation wire guide wire lumen  386  is included within tube  384 , as illustrated in FIG. 22. A separate guide wire may be required for this embodiment, to guide the radiation emitting device through to the balloon assembly. A guide wire may be required to provide a pilot wire through the rise or bend  362  in the radiation wire tube, where the guide wire lumen enters the balloon assembly, where it may be difficult to push a flexible tube. 
     One embodiment includes perfusion holes proximal of coil  382 , providing perfusion through lumen  386  when the guide wire is retracted. In this embodiment, the guide wire can be used to position the radiation member then retracted proximal of radiation wire tube rise  362 , lessening the obstruction to perfusion blood flow during irradiation. The radiation member having perfusion holes is optimally used in conjunction with an open ended radiation tube, described below. Radiation wire coil  382  preferably includes Yttrium-90 or Nickel-66, high energy beta emitters. In another preferred embodiment, radiation wire  382  includes Gadolinium-153, a gamma emitter. 
     Referring now to FIG. 23, another embodiment catheter  390  is illustrated. Catheter  390  is similar to catheter  320 , but has a radiation wire tube  392  with an open distal end  394 . The resulting perfusion lumen  356  is still open to passage by the radiation wire, which can extend substantially through the balloon assembly, but without a supporting tube in this distal region. As can be visualized with FIG. 19, the removal of radiation wire tube  358  would provide greater cross sectional area for perfusing blood flow within perfusion lumen  356 . The greater cross sectional area would be especially significant during periods when the radiation wire device itself is not within the perfusion lumen, as when the radiation wire device lies proximal of radiation wire tube bend  362 . A device having no radiation wire tube within the inflatable balloon also provides a smaller profile for the balloon assembly in the deflated state, as can be illustrated by visualizing FIG. 19 without radiation wire tube  358 . The open ended radiation wire lumen does allow contact between the radiation source and the bodily fluids. This may require sterilization or disposal of the radiation source after a single use. 
     As previously stated, a preferred source of radiation for all embodiments of the present invention is the radioactive compound Nickel-66. Nickel-66 decays with a half life of 2.28 days with only low energy beta emissions and no gamma emission into its daughter element Copper-66. Copper-66 then emits high energy beta radiation with a half life of 5.10 minutes and decays into the stabile element Zinc-66. This two-step decay has a particular advantage in use in the catheters of the present invention. 
     The Nickel-66 acts as a carrier for the high energy copper decay allowing for time to transport the source to the end user, and also allows for disposal of the device through ordinary means in about 23 days. A Copper-66 source alone would decay quickly and not be useful without the parent Nickel. Nickel is low cost and has desirable mechanical properties in its pure form and in alloys, such as a Nickel Titanium alloy. 
     The Nickel-66 can be utilized in any of the embodiments disclosed herein. Also, this source or another source could be incorporated into an atherectomy device. An exemplary embodiment of an atherectomy device is disclosed by Auth et al., in U.S. Pat. No. 5,314,407, the disclosure of which is incorporated herein by reference. A rotating ablative burr assembly is utilized to remove a stenosis. This burr assembly can have incorporated therein a radiation emitting source. Thus, radiation treatment can occur simultaneously with the atherectomy procedure. 
     Another preferred radiation source is Gadolinium-153. Gadolinium-153 is a composite gamma source which can provide low energy gammas to vessel intima layer while providing higher energy gammas to penetrate calcified plaques and reach the adventitia. Moderate shielding can be used with Gadolinium-153, allowing the treating physician to remain in the room with the patient during therapy. Another preferred source of radiation can include Yttrium-90, a high energy beta emitter. 
     Numerous advantages of the invention covered by this document have been set forth in the foregoing description. It will be understood, however, that this disclosure is, in many respects, only illustrative. Changes may be made in details, particularly in matters of shape, size, and arrangement of parts without exceeding the scope of the invention. The inventions&#39;s scope is, of course, defined in the language in which the appended claims are expressed.

Technology Classification (CPC): 0