Abstract:
Radioactive sources for implanting in tissue to treat tumors and to provide a directional dose to allow improved dose placement, particularly at the interface between healthy and diseased tissue.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS  
       [0001]     This application is based on provisional application 60/572,962 filed May 20, 2004 entitled “Directionally Emitting Radioactive Sources for Permanent Implantation”. 
     
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT  
       [0002]     This invention was made with United States government support awarded by the following agencies: DOE DE-FG07-01ID14104. The United States has certain rights in this invention. 
     
    
     BACKGROUND OF THE INVENTION  
       [0003]     The present invention relates to radiation therapy principally for the treatment of cancer and benign diseases, and in particular, radioactive sources used in one radiation therapy technique termed brachytherapy.  
         [0004]     Brachytherapy is radiotherapy where small, radioactive sources are placed into diseased tissues, in body cavities near disease, or in contact or close proximity to disease. Brachytherapy takes many forms, the most common of which are permanent implants, where the sources are left in place from the time of implantation for the life of the patient, or temporary implants, where the sources dwell in the treatment location for a specified time, after which they are removed. The temporary implants may be low dose-rate, where the sources stay in place for times on the order of a day to a week, or high dose-rate, where a treatment takes a matter of minutes. There is also a middle dose-rate region where treatments range from a couple of hours to just over a day.  
         [0005]     One common example of a permanent implant occurs with treatment of cancer of the prostate. Prostate permanent implant brachytherapy is a radiation treatment technique in which radioactive sources are implanted directly into the prostate and left in place permanently. Typically, 50 to 100 small radioactive sources are implanted near the tumorous tissue.  
         [0006]     The sources may be radioactive material absorbed onto small resin spheres contained within a titanium capsule or on the surface of a silver rod also sealed in titanium. The sources often use iodine-125 as the source material for the radiation, which has a half-life of approximately sixty days providing an average energy of emitted photons of approximately 27 keV, with commercial source strengths in the range of 0.2-1.0 mCi.  
         [0007]     The sources, of a size 0.8 mm in diameter and 4.5 to 5 mm long, may be implanted using a hollow needle. The needle provides a lumen 1.3 to 1.5 millimeters in diameter and about 20 cm long into which the sources may be inserted along with spacers controlling their separation. The loaded needle is inserted into the patient, and then withdrawn, while a plunger ejects the contained sources.  
         [0008]     The location of the radioactive sources is desirably selected to provide a prescribed dose to the diseased tissue of the prostate while sparing surrounding sensitive, critical tissue, for example, the urethra and rectum. Source placement in the region between sensitive tissue and diseased tissue is a compromise between providing sufficient dose to the diseased tissue and minimizing dose to the sensitive tissue.  
         [0009]     Prostate cancer can also be treated using high dose-rate brachytherapy. In this case, needles are placed into the prostate and then connected to a treatment unit. The unit moves a very intense radioactive source through the needles, stopping at determined positions for times calculated to deliver the desired dose. The device steps the source through the first needle, retracts it and then moves the source through the next needle. This pattern continues until all needles have been accessed by the radioactive source and the treatment is concluded.  
         [0010]     Many cancers are treated in a manner between the two described, where needles are placed into the target, and many sources are placed into the needles, with source strengths and positions calculated to deliver the desired dose in the prescribed time. The dose pattern emitted by these sources is isotropic relative to the lengthwise axis of the encapsulated cylindrically shaped source.  
       BRIEF SUMMARY OF THE INVENTION  
       [0011]     The present inventors have developed a radioactive source having a directional radiation emission pattern that allows improved treatment of tissue at the interface between diseased and healthy, radiation-sensitive tissue. Orientation and retention of the sources in the desired orientation may be provided by external features on the sources serving to anchor the sources or orient them within the needle.  
         [0012]     Specifically, the present invention provides a brachytherapy source for radiation treatment providing directional emission of radiation.  
         [0013]     It is thus one object of at least one embodiment of the invention to provide improved control of a radiation dose providing sources with directional radiation emission patterns.  
         [0014]     The directionality may provide a minimum emitted radiation at a first angle and a maximum emitted radiation at a second angle opposite the first angle.  
         [0015]     Thus it is another object of at least one embodiment of the invention to provide sources uniquely suited for the region between healthy and tumorous tissue that can be used to create a sharper boundary in treatment between these two zones.  
         [0016]     The sources may be adapted to slide through a needle for implantation with a longitudinal axis of the source extending along a lumen of the needle. The radiation may be directional in a plane perpendicular to the longitudinal axis so that rotation of the needle may orient the directionality of emission.  
         [0017]     It is thus another object of at least one embodiment of the invention to provide a simple method of placing and orienting the sources.  
         [0018]     The source may be comprised of a radioactive source with a shield partially blocking radiation from the radioactive source.  
         [0019]     It is thus another object of at least one embodiment of the invention to provide a simple method of shaping the emission of the source using a shield.  
         [0020]     The radioactive source and shield may be encapsulated in a biocompatible radiation permeable casing that does not follow the shape of the source and shield.  
         [0021]     Thus it is another object of at least one embodiment of the invention to provide independence between the shape of the shield and radiation source and the shape of the source, the latter, which may be shaped for improved insertion, orientation, and retention.  
         [0022]     The shield and source may be shaped and arranged with respect to each other to substantially maximize within material constraints a rate of change of emissions as a function of angle about the source.  
         [0023]     It is thus another object of at least one embodiment of the invention to provide a large gradient in radiation with respect to angle for at least a portion of the radiation pattern for the source.  
         [0024]     The source, when adapted to slide through a needle for implantation with a longitudinal axis of the source extending along a lumen of the needle, may be directional in a transverse plane perpendicular to the longitudinal axis.  
         [0025]     It is thus another object of at least one embodiment of the invention to provide a method of controlling the angle of implanting of the sources with a needle.  
         [0026]     The source may include at least one outwardly extending vane, guide, or anchor.  
         [0027]     It is thus another object of at least one embodiment of the invention to provide a method of anchoring the sources against rotation in the patient for permanent implants. In another embodiment the outwardly extending vane can serve as a guiding mechanism for temporary implants as the source passes through a needle or catheter.  
         [0028]     The vane may be fixed or expandable outward. In one embodiment, the vane is fixed to the source jacket or part of the jacket and remains extended at all times. In one embodiment, the vane may be soluble so as to dissolve after a period of time. In another embodiment, the vane may be a wire expanding from the source after insertion.  
         [0029]     It is yet another object of at least one embodiment of the invention to provide several methods of rotationally stabilizing the source without hampering initial insertion of the source in tissue.  
         [0030]     These particular objects and advantages may apply to only some embodiments falling within the claims and thus do not define the scope of the invention. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0031]      FIG. 1  is a fragmentary cross-sectional view taken along a mid-sagittal plane of a patient receiving radioactive sources for the treatment of the prostate;  
         [0032]      FIGS. 2   a  and  2   b  are superimposed perspective and transverse cross-sectional views, respectively, of a radiation source of the prior art, showing the pattern of radiation emission;  
         [0033]      FIG. 3  is a transverse cross-sectional view through a source of the present invention showing a shield layer between a core of radioactive material and an outer sheathing;  
         [0034]      FIG. 4  is a cross-sectional view similar to that of  FIG. 3  showing optimization of the core and shield to provide sharper demarcation in the emission zones;  
         [0035]      FIG. 5  is plot of relative dose as a function of angle about the source within a transverse plane for the sources of  FIGS. 3 and 4 ;  
         [0036]      FIG. 6  is a figure similar to that of  FIG. 2   b  showing the emission pattern for the source of  FIG. 4 ;  
         [0037]      FIG. 7  is a cross-section through the patient along an anatomical horizontal plane, showing placement of the multiple sources of the present invention in a ring about the urethra facing into the prostate;  
         [0038]      FIG. 8  is a perspective view and cross-sectional expansion of a needle used for placing the source of  FIG. 4 ;  
         [0039]      FIG. 9  is a cross-section similar to that of  FIGS. 3 and 4  showing use of a keel to prevent source rotation; and  
         [0040]      FIG. 10  is an exploded perspective view of an alternative embodiment of the source laterally expanding wire wings that press into the tissue to prevent rotation of the source and showing an insertion needle for inserting that source and a retractor hook used for removing or reorienting that source. 
     
    
       [0041]     The above figures depict the embodiment of permanent implant brachytherapy and the delivery of the sources in this embodiment. Another embodiment is temporary implant brachytherapy. For this embodiment, the source design is essentially the same, however, the procedure for delivery is different and has been discussed in the background section. Another embodiment is for high dose-rate brachytherapy, in which embodiment the source is connected to a cable as discussed in the background section.  
       DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT  
       [0042]     The detailed description describes permanent implant brachytherapy, however it will be understood to those of ordinary skill in the art that the sources and needles described may also be adapted for temporary implant brachytherapy as discussed in the previous section.  
         [0043]     Referring now to  FIG. 1 , a prostate brachytherapy uses a hollow needle  10  to place radioactive sources  12  within the prostate  14  transperineally.  
         [0044]     The needle  10  may be guided by a plate  16  having a plurality of holes  18  placed at regular grid locations over the two dimensions of the plate  16 . The plate  16  may be clamped to a transrectal ultrasonic probe  22  providing an ultrasonic beam  24  illuminating the prostate  14 . The beam  24  provides a means of verifying the depth of placement of the sources  12  as they are ejected from the needle  10  by means of a plunger  26  fitting within the hollow shaft of the needle  10 . In one technique, the sources  12  are placed within the needle  10  in a preconfigured separation enforced by non-radioactive spacers.  
         [0045]     Referring now to  FIG. 2 , each of the sources  12  used in the prior art is roughly cylindrical in shape, the axis of the cylinder (termed henceforth “the longitudinal axis  20 ”) aligning with the axis of a lumen of the needle  10  when the source  12  is placed within the needle  10 .  
         [0046]     A longitudinal radiation dose  28 , defined by an isodose line lying in a plane along the longitudinal axis  20 , is substantially symmetric about the source  12 . In addition a transverse radiation dose  30  defined in a plane perpendicular to the longitudinal axis  20  is likewise symmetric, and in this case, circular. By symmetrical, it is meant that there exists a point were some measure of the dose (e.g. the distance from the point to an isodose line) is equally balanced on opposite sides of the point at all angles of interest. For the longitudinal radiation dose  28 , the angles of interest are those laying in the relevant longitudinal plane for the transverse radiation dose  30 , and the angles of interest are those lying in the relevant transverse plane.  
         [0047]     Referring now to  FIG. 3 , a directionally emitting source  32  per the present invention provides a core radioactive source  34  positioned within a shell  36  of titanium or other biocompatible material. The source  34  may, for example, be a non-radioactive substrate material such as silver, polymer, or graphite coated with a radioactive material such as I-125 or Pd-103.  
         [0048]     In a first embodiment, the shell  36  and source  34  are generally cylindrical. Positioned between the source  34  and the shell  36  is a shield  38 , in this case, covering approximately 180 degrees of the cylindrical circumference of the source  34 . Radiation emitted from the upper surface of the source  32  (designated as an azimuthal angle of zero degrees) is substantially unattenuated by the shield  38  whereas the shield  38  significantly reduces radiation emitted through the lower surface of the source  32 . Generally, a variation in dose in excess of 5 to 1 may be obtained with reasonable shield thicknesses. A variation in radiation emission of at least 50% is preferred.  
         [0049]     Referring now to  FIG. 4 , in an alternative embodiment, the circular cross-sectional areas of the source  34 , the shell  36 , and the accurate shape of the shield  38  are altered to sharpen the transition between the attenuated radiation from the bottom of the source  32  to the top of the source  32 . This sharpening may be optimized through computer modeling, but in this embodiment, generally concentrates the radioactive surface area of the source  34  near the shield  38  and flattens the shield  38  so that the shield  38  diverges tangentially from the source  34  rather than wrapping around the source  34  in a cylindrical trough as per  FIG. 3 .  
         [0050]     Referring to  FIG. 5 , a plot of relative dose (RD) as a function of azimuthal angle shows an optimized curve  40  produced by the source  32  of  FIG. 4  having a steeper slope (i.e., rate of change of relative dose as a function of azimuthal angle) than unoptimized curve  42  produced by the source  32  of  FIG. 3 . This optimized curve  40  allows sources  32  to create a radiation dose pattern that more finely distinguishes between tissue that receives radiation and tissue that has minimal radiation exposure.  
         [0051]     Referring to  FIG. 6 , a transverse radiation dose  30 ′ for the sources  32  of  FIGS. 3 and 4  is directional in the transverse plane in contrast to the symmetrical and circular transverse radiation dose  30  shown in  FIG. 2   b  for the prior art.  
         [0052]     Referring now to  FIG. 7 , sources  32  of the present invention, properly oriented, can provide a desired therapeutic dose of radiation to the prostate  14  while minimizing radiation dose to the urethra  44 . In one example, the sources  32  are placed along a circular arc in tissue near an interface between the prostate  14  and the urethra  44 , the arc having an open portion above the rectum  45 . The front surfaces of the sources  32  defined by zero azimuthal angle are positioned to face outward away from the urethra  44 .  
         [0053]     The sources  32  may, for example, be integrated into conventional treatment planning by first placing the sources  32  as described, and then adding prior art sources  12  based on the fixed position of the initial sources  32 . Multiple sources  32  may be placed in a needle  46  ( FIG. 8 ) for implantation. The needle  46  may also hold standard sources  12  which may be specially prepared to have the same shape as the lumen of the needle  46  or which may have a different shape that nevertheless fits within the lumen of the needle  46  without fully conforming to the interior of the lumen. After each source  32  is ejected from the needle  46  by a plunger, the needle may be repositioned by drawing it along the needle axis and/or rotating the needle.  
         [0054]     Referring now to  FIG. 8 , the sources  32  may be oriented by using a special needle  46  having a lumen with an asymmetric or noncircular cross-section  48  keyed to features of the source  32  (for example, conforming to the asymmetric cross-section of the source  32 ) to prevent rotation of the source within the needle  46 . Indicia  50  may be placed on the needle  46  to indicate the zero azimuthal angle of the sources  32  as they are inserted within the needle  46 . Insertion of the needle  46  into the patient may thus be with a controlled orientation or the needle  46  may be rotated after insertion or between discharge of various sources to control the orientation of those sources  32 .  
         [0055]     Generally the needle  46  may be simply extruded according to the outline of the cross-section of the sources  32  in the transverse plane and thus may have an outer surface generally conforming to the cross-section of the lumen with constant wall thickness. Alternatively, the outer surface may adopt an alternative cross-section, for example, a cylindrical cross-section or the like.  
         [0056]     Referring now to  FIG. 9 , the source  32  may stably resist rotation within tissue of the patient based on its asymmetric outline or other anchoring mechanisms. In one embodiment, the anchoring mechanism may be the addition of a transversely extending keel  52  or fin that may engage tissue to prevent axial rotation of the source  32 . The keel  52  may be formed integrally with the shell  36  or may be added in a later manufacturing step. In one embodiment, the keel or fin  52  may be a biodissolving material that provides stabilization until scar tissue can lock the source  32  into position. In one embodiment, the keel or fin  52  may serve as a guide for temporary implant sources.  
         [0057]     Referring now to  FIG. 10 , the stabilization mechanism for the source  32  need not be fixed, but may comprise extensible wings  54  formed in one embodiment from “shape memory” wire (an NiTi alloy) or spring wire either that may crush inward slightly when the source  32  is inserted into the needle  46  and then spring outward to engage tissue with an outward biasing force. The lumen of the needle  46  may be adjusted appropriately to accommodate these anchoring mechanisms.  
         [0058]     In the embodiment of  FIG. 10 , the outwardly extending wings  54  provide a location by which to grip the source  32  with a retractor tool  56  having a pair of hooks  58  that may engage the wings  54  when extended for withdrawal of the source  32 . In the example of  FIG. 10 , the force of the hooks  58  on the wings  54  is such as to retract the wings  54  somewhat to improve their movement through the tissue.  
         [0059]     The present invention is not limited to use with the prostate, but may be used in any brachytherapy source application. Other applications include breast, lung, esophagus, larynx, and gynecological applications.  
         [0060]     It is specifically intended that the present invention not be limited to the embodiments and illustrations contained herein, but include modified forms of those embodiments including portions of the embodiments and combinations of elements of different embodiments as come within the scope of the following claims.