Abstract:
A manifold system allows for the movement of a radioactive fluid from a container to a treatment balloon or other device, and the withdrawal of the radioactive fluid from the treatment device. The system allows for the convenient movement of the fluid, with minimal radiation exposure for those using the system. The manifold system is particularly useful in the use of radiation to prevent restenosis of arteries.

Description:
This Application claims benefit of Prov. No. 60/131,957 filed Apr. 3, 1999. 
    
    
     BACKGROUND OF THE INVENTION 
     This invention relates to an apparatus and method for manipulation of a radioactive fluid. This invention also relates to a method of treating stenosis (blocked arteries) and preventing restenosis (re-blocking of the artery) which employs a radioactive fluid. 
     It is often desired to safely manipulate a radioactive fluid. For instance in oncology, it may be necessary to introduce a radioactive fluid into the body of a patient in for diagnostic or therapeutic purposes. Specifically, a radioactive fluid might be injected into the bloodstream or into a tumor. Alternatively, a radioactive fluid might be introduced into a balloon catheter in order to irradiate tumor cells or other cells. 
     Percutaneous transluminal angioplasty (PTA) is the general technique of dilatation of a blocked artery (both peripheral and coronary (PTCA) arteries) with mechanical means at the end of a catheter. The use of a balloon catheter in PTA is well known. The catheter is positioned with the balloon at the site of the blockage, typically with the assistance of a guide wire and a fluoroscope, and the balloon inflated at high pressure (e.g.: 6 to 20 atmospheres (0.6 to 2 MPa). 
     While the use of a balloon catheter in PTA is an effective technique, it is common for the affected artery to become re-blocked in a period of several (typically 3-6) months (“restenosis”). Restenosis is believed to occur as a result of injury to the arterial wall during the PTA procedure. One approach to treating restenosis is to repeat the PTA procedure. However, the expense of PTA and the inconvenience to the patient make this undesirable. An attempt at preventing restenosis is the use of a stent, which is a small, typically metal device that holds the artery open. Stents, however, are only partially effective in preventing restenosis. 
     An approach that appears to be quite promising is the use of radiation to prevent restenosis. In doses of 8 to 30 Gy, radiation has been shown to be relatively safe and effective in preventing restenosis. While the exact mechanism of action is not known, it is suspected that the radiation “stuns” the cells that cause restenosis, rendering them less able to re-block the artery. 
     Several approaches have been taken to supplying radiation to the affected site. One is the use of a solid radioactive source (such a beads) fixed in the end of a catheter. After PTA, the PTA catheter would be removed and the radioactive catheter inserted. This technique suffers from the disadvantage of making it difficult to center the radioactive source in the artery so that the artery is uniformly irradiated. Another disadvantage is that the catheter is radioactive the entire time it is in use, causing exposure issues for the patient and the medical personnel. 
     Another approach is to position a guide wire past the obstruction, slide a balloon catheter over the guide wire to the obstruction, inflate the balloon to perform the angioplasty, remove the guide wire, and replace it with a wire having a radioactive tip. This approach also suffers the disadvantages of difficulties centering the radiation source and the fact that the treatment wire is radioactive during the entire time it is in use, as well as problems associated with removing the guide wire, which may complicate response to a sudden collapse of the artery. 
     A technique that results in uniform irradiation is the use of a balloon catheter filled with a radioactive fluid, generally a liquid. This method has the advantage of ease of use, including automatic centering of the radiation. Further, since the catheter is not radioactive until after it is inserted into the patient, there is far less undesired radiation exposure for the patient and the medical personnel. 
     U.S. Pat. No. 5,199,939 (Dake) teaches a general method of preventing restenosis by supplying a source of radiation at the end of a catheter to the affected vessel. Dake uses radioactive pellets at the end of a catheter having variable stiffness along its length. 
     U.S. Pat. No. 5,195,962 (Martin; Vas-Cath Incorporated) describes a catheter with 3 non-concentric lumens, and a method of manufacturing such a catheter. The central lumen of the catheter can be used for a guide wire. This reference discloses several other multi-lumen catheters. 
     U.S. Pat. No. 5,207,648 (Gross; The Kendall Company) describes a catheter with 3 concentric lumens. 
     U.S. Pat. No. 5,226,889 (Sheiban) discloses a catheter having 2 balloons where the distal balloon is used to open an artery and the second, of larger diameter, is used to implant a stent. 
     U.S. Pat. No. 5,314,409 (Sarosiek; UVA Patents Foundation) teaches an esophageal perfusion catheter having two balloons and multiple lumens. Some of the lumens communicate with ports between the balloons. 
     U.S. Pat. No. 5,342,306 (Michael) is representative of several disclosures that show two balloons used to isolate a treatment area in an artery so that liquid can be introduced into the space between the balloons without being washed away by blood flow. 
     WO 96/17654 (Thornton; Omnitron International) teaches the use of a balloon catheter filled with a radioactive liquid. In one embodiment Thornton uses multiple concentric balloons to guard against leakage, etc. In another embodiment Thornton uses a main balloon and two additional balloons on either side of the main balloon to block the flow in the artery in case of rupture of the main balloon, thus preventing flow of radioactive liquid throughout the patient&#39;s body. 
     WO 97/48452 (Lavie; The State of Israel, SOREQ) teaches a device for preventing restenosis with beta radiation from a Rhenium-186 or Rhenium-188. This reference employs several embodiments that place the radiation at the end of a catheter. 
     WO 98/46309 (Pipes; Mallinckrodt) teaches a double serial balloon in which one balloon is used to perform angioplasty and a second balloon on the same catheter is used to perform the radiation treatment. 
     SUMMARY OF THE INVENTION 
     Briefly, the invention comprises a manifold system for manipulating a radioactive fluid. The apparatus and method are particularly suitable for use with a balloon catheter and a radioactive liquid to prevent restenosis. The manifold system provides a convenient and relatively safe method of handling the radioactive fluid. The invention also comprises a method of sequentially removing a radioactive fluid from a container and introducing it into a catheter or other apparatus. The apparatus and method allow for the quick, convenient, and relatively safe radiation treatment of stenosed arteries without the drawbacks associated with many other techniques. The apparatus of the invention can also be used for other situations involving the handling of a radioactive liquid, such as the use of a balloon catheter filled with a radioactive liquid for use in tumor therapy. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a perspective view of a manifold assembly. 
     FIG. 2 is a is a view of the front half of the manifold assembly of FIG.  1 . 
     FIG. 3 is a is a view of the back half of the manifold assembly of FIG.  1 . 
     FIG. 4 is a perspective view of a container shield. 
     FIG. 5 is a sectional view of the container shield of FIG. 4, taken through section lines  5 — 5 . 
     FIG. 6 is a schematic view of the a manifold assembly and associated components. 
     FIG. 7 is a sectional view of the lower portion of the manifold assembly of FIG. 1 with a container shield and container in place. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     In this specification and claims, numerical values and ranges are not critical unless otherwise stated. That is, the numerical values and ranges may be read as if they were prefaced with the word “about” or “substantially”. 
     Referring first to FIG. 1, a manifold assembly  11  has a housing  13  having a front portion  15  and a rear portion  17 . Extending through the face of the front portion  15  are pressure knob  21  and fluid knob  23 . Surrounding inlet knob  21  and fluid knob  23  are indica  25  to inform the user of the relative position of the knobs. When in an upright position, manifold assembly  11  rests on its bottom surface  27 . 
     At the top of manifold assembly  11  is a pressure port  31 , which is illustratively a luer connection of the type commonly found on medical equipment such as syringes. 
     In FIG. 2, the inside of front portion  15  of manifold assembly  11  is shown. The major parts of front portion  15  include an outer shell  33 , and inner shell  35  and a lead shield  37  which fits between outer shell  33  and inner shell  35 . Additional lead shielding is present at top shield  41  and bottom shield  43 . 
     Also visible inside front portion  15  are the insides of pressure knob  21  and fluid knob  23 . The inside face of pressure knob  21  has groves  22  and the inside face of fluid knob  23  has groves  24 , which correspond to valve handles (described below). Ratchet  45  pivots on a central pin  46  and is rotated by spring  47  so that pawl  48  engages gaps  49  spaced along the outer periphery of fluid knob  23 , permitting fluid knob  23  to be rotated in only one direction (clockwise, as viewed from the perspective of FIG.  1 .). 
     The bottom surface  27  of front portion  15  is open to receive a vial seated in a container shield (both described below). Pins  51  engage gaps on the container shield to retain it in place (described below). Grommet  53  is attached to inner shell  35 . 
     Referring now to FIG. 3, rear portion  17  of manifold assembly  11  is shown. The major parts of rear portion  17  include an outer shell  33   a , and inner shell  35   a  and a lead shield  37   a  which fits between outer shell  33   a  and inner shell  35   a . Additional lead shielding is present at top shield  41   a  and bottom shield  43   a . Pins  51   a  are identical to those shown in FIG.  2 . 
     A manifold  55  has a manifold tube  57  having a circular cross section. A plug  59  is slidably received in the interior of tube  57 . Manifold tube  57  rests in an inner shield  81  made from a plastic block  83  and lead strips  85 . A half grommet  53   a , along with half grommet  53  (FIG. 2) supports manifold tube  57 . 
     A pressure path  61  is defined by a pressure tube  63  which terminates at pressure port  31 . Pressure tube  63  is curved and passes through an opening defined by top shields  41  and  41   a  in order to limit the amount of radiation that is able to exit near the top of manifold assembly  11 . Pressure valve  65  connects the upper end of manifold tube  57  to pressure tube  63 . Pressure valve  65  has a handle  66  which mates with groves  22  of pressure knob  21  (FIG.  2 ). 
     A fluid valve  67  has a handle  68  which mates with groves  24  of fluid knob  23 . Fluid valve  67  connects the lower end of manifold tube  57  to inlet path  69  and outlet path  71 . 
     Inlet path  69 , as illustrated, is a direct connection of hollow needle  73  by means of a luer connection  75 . A binding ring  87 , tightened by a screw  89 , prevents needle  73  from being pushed vertically upward into housing  13 . Outlet path  71  is an outlet tube  77  that allows fluid valve  67  to communicate with outlet port  79 . 
     Turning now to FIGS. 4 and 5, a container shield  101  has a hollow cylindrical outer shell  103  that mates with an inner shell  105 . A lead shield  121  is sandwiched between outer shell  103  and inner shell  105 , and a resilient pad  123  lies at the bottom of inner shell  105 . A rubber grommet  117  lies in a groove  119  at the top of inner shell  105 . Outer shell  103  is connected to a base  107  which include a resilient sub-base  109 . Four locking flanges  111  are evenly spaced around the outside of hollow cylindrical portion  103 . Each locking flange  111  defines a locking detent  113 . The underside  115  of each locking flange  111  is angled to be closer to base  107  near locking detent  113  and farther from base  107  away from locking detent  113 . 
     FIG. 7 shows container shield  101  in locking relationship with rear portion  17  of housing  13 . To effect the locking relationship shown in FIG. 7, a glass vial  131  is inserted into container shield  101  where it rests on resilient pad  123 . With container shield  101  sitting on a firm surface, housing  13  is lowered onto container shield  101 , so that needle  73  punctures the rubber seal  133  which is held in place with metal cap  133  and grommet  117  will contact a portion of inner shell  35  and  35   a , forming a liquid-tight seal. Housing  13  is then rotated about its longitudinal axis, so that pins  51  and  51   a  are pushed slightly downward by the underside  115  of locking flange  111 , until they are directly under locking detent  113 , where they move to lock container shield  101  to housing  13 . When this locking relationship exists, the tip of needle  73  is at the bottom of vial  131  so as to be able to withdraw essentially all of the liquid in vial  131 . 
     Pressure port  31  is connected to a means of providing fluid pressure (preferably a gas such as air) at pressures of about 0.1 to 0.4 MPa. Although a simple syringe could be used, preferred is a screw syringe of the type commonly used for angioplasty. A Model 2030 syringe made by ACS is an exemplary source of pressure. The pressure source also preferably includes a means for at least one of measuring the pressure, measuring the duration of a treatment, warning of a pressure exceeding a preset limit, or warning of a sudden los of pressure (which would indicate a leak in the system). 
     Outlet port  79  is connected to a radiation treatment balloon, which may be specially made for this application, or may be an ordinary balloon catheter of the type commonly used for angioplasty. 
     The manifold is designed such that it can be operated a number of different ways. However, the following method is believed to be optimal. To begin, pressure valve  65  is closed and fluid valve  67  is positioned to connect outlet path  71  and manifold tube  57 . 
     FIG. 6 shows a schematic representation of the manifold system of the invention. Manifold tube  657  is connected at one end to pressure path  661  via pressure valve  665  and at the other end to vial  698  and outlet port  679  via fluid valve  667 . Outlet port  679  connects to the treatment balloon  697 , passing through vacuum valve  696  which also connects to vacuum source  695 . Adjacent to valves  665 ,  667 , and  696  are schematic diagrams of the positions of the valves for various operating conditions. 
     EXAMPLE I 
     A human patient with a stenosed coronary artery was prepared for angioplasty by making an incision in the femoral artery. With the assistance of a fluoroscope, a guide wire was positioned past the stenosed region. A balloon catheter was fed onto the guide wire and advanced to the site of the stenosis. Diluted Hexabrix® X-ray contrast media (from Mallinckrodt Medical, Inc.) is forced out of an inflator syringe by hand to inflate the balloon to 1.5 MPa, opening the artery. The balloon was then deflated and the catheter withdrawn from the patient. 
     The radiation treatment procedure began with a device generally as described above, with vial  698  connected to fluid valve  667 , pressure valve  665  in position C, fluid valve  667  in position  1 , vacuum valve  696  in position A, and the manifold assembly  11  in an upright position. Treatment balloon  697  was inspected, tested, connected to the manifold assembly  11  via vacuum valve  696 , and inserted into the patient. 
     Vacuum source  695  (a vacuum syringe) was activated and a vacuum drawn in treatment balloon  697  and manifold tube  657 . Vacuum valve  696  was then turned to position B and the vacuum source  695  disconnected (the vacuum source will not be used further in a normal procedure, but may be used for emergency removal of radioactive fluid from the treatment balloon  697  in the event of failure of other components of the system). 
     Fluid valve  667  was then turned to position  2 . The vacuum in the system caused the radioactive fluid in vial  698  to be drawn into manifold tube  657 . After waiting a moment to ensure that all fluid movement has stopped, fluid valve  667  was then turned to position  3 . This caused some of the radioactive fluid to move into treatment balloon  697 . Fluid valve  667  was then turned to position  1 , disconnecting the vial from the system. 
     Pressure source  699  (a screw-type syringe as described above) was attached to the system via pressure path  661  and pressure valve  665 . Pressure valve  665  was then turned to position O. As pressure was applied by pressure source  699 , treatment balloon  697  inflated, dosing the artery with radiation. Because the treatment blocked blood flow to the patient&#39;s heart, the treatment was interrupted to allow blood flow by reversing pressure source  699 , deflating treatment balloon  697 . After a few minutes, the treatment was resumed by again activating pressure source  699  to reinflate treatment balloon  697 . 
     When the treatment was complete, pressure source  699  was again reversed and treatment balloon  697  deflated. Fluid valve  667  was turned to position  2  and pressure source  699  activated to force the radioactive fluid from manifold tube  657  into vial  698 . To ensure complete removal of the radioactive fluid from treatment balloon  697 , fluid valve  667  was turned to position  1 , pressure source  699  was reversed, fluid valve  667  was turned to position  2 , and pressure source  699  activated. Finally, fluid valve  667  was turned to position  1  and pressure valve  665  turned to position C. Treatment balloon  697  was then be withdrawn from the patient and the system disposed of in a manner consistent with the amount of radiation present. 
     EXAMPLE II 
     (Hyptothetical) 
     The procedure of Example I was repeated, except that plug  59  in manifold tube  63  is porous rather than solid. By “porous” is meant that when dry, it will allow gasses to pass through it, but it will not allow liquids to pass through it. Thus, instead of using vacuum valve  696 , vacuum source  695  is attached to pressure valve  665 . Since plug  59  is porous, the air in the system passes through plug  59  to vacuum source  695 . 
     As can be seen from the above, the manifold of the invention minimizes the amount of radioisotope needed for a procedure, and minimizes the hazards associated with manipulating a radioactive fluid.