Abstract:
Methods and apparatus are described for irradiating living tissue via a cavity or lumen, using an inflatable balloon applicator. In a preferred embodiment the applicator balloon has a balloon skin with x-ray contrast material in relatively low concentration, so that an outline of the balloon will appear sharply when imaged externally. In another preferred embodiment the balloon catheter has a drain for withdrawing liquids from the cavity, which may include channels or texture on the exterior of the balloon. Methods are described for using a switchable miniature x-ray tube, variable as to voltage and current, to achieve accuracy in an isodose profile.

Description:
BACKGROUND OF THE INVENTION  
       [0001]     This application is a continuation in part of application Ser. No. 10,683,885, filed Oct. 13, 2003, now 
     
    
       [0002]     This invention concerns therapeutic radiation treatment of living tissue, usually but not necessarily within a body cavity, which may be a surgical cavity following a resection of a tumor. In one aspect the invention is concerned with use of a switchable, miniature electronic x-ray source, which may be controllable as to depth and intensity, for administering such therapeutic treatment.  
         [0003]     Treatment of surgical cavities, such as after malignant tumor excision, has been accomplished with applicators which are inserted usually into a newly formed opening through the skin, a conveniently located opening into the surgical resection cavity. Generally the location is different from the surgical closure itself. Applicators have been disclosed which essentially comprise a balloon of known and relatively rigid geometry, essentially spherical, expandable generally to about four to six centimeters, that is, designed to have an inflated size of about four to six centimeters diameter. Some of the generally spherical balloon catheters were described as having multiple walls to form inner and outer spaces, for reasons relating to the objective of delivering a uniform dose to tissue surrounding the balloon. In the prior art such known-geometry balloons were inflated with a liquid, with an applicator guide positioned within the balloon and in the liquid, so that the applicator guide could receive a radiation source comprising a radioactive isotope.  
         [0004]     With balloons limited to known geometries, there are limitations in the ability to treat a cavity margin thoroughly. In some cases, the patient cannot take advantage of such a treatment protocol because the known-geometry balloon applicator simply cannot fill many surgical cavities that are irregular in shape. Other measures have to be used in those cases, such as external radiation therapy.  
         [0005]     Another limitation of known procedures using balloon catheters is in regard to locating the balloon correctly within a cavity of the patient, such as a resection cavity. The saline solution used to inflate the balloon contains contrast material which will be visible by taking an external x-ray. With the contrast material contained in the balloon&#39;s solution, the surgeon or technician can detect a pale “shadow” in the x-ray to determine the location of the balloon and to correct its position if needed. The procedure typically calls for use of the contrast material at about 3% in the saline solution. Dose planning for the known-geometry balloon is based on specific concentration of contrast. However, because the balloon shape is difficult to see in the x-ray, surgeons usually add the contrast material in a much higher concentration, not as contemplated by the dose plan, so as to better detect the balloon in the x-ray. The concentration may be up to about 20%-30% in practice. As a result, the therapeutic radiation from the x-ray source placed into the center of the balloon becomes attenuated to the extent that the actual dose profile received in a patient&#39;s tissue may be significantly less than the prescribed dose.  
         [0006]     The use of isotopes has been the practice in administering x-ray radiation to patients prior to the present invention. The isotopes must be handled carefully and reliably shielded between uses. With the isotopes they are always “on”, and only one setting is available for all dwell locations where a dose is to be administered. In many cases it would be convenient to have a better procedure and source that would allow modulation and more accurate dose delivery.  
       SUMMARY OF THE INVENTION  
       [0007]     The invention now disclosed provides improved procedures for therapeutic radiation treatment of tissue, which may be following resection of a tumor or which may involve administering the radiation within an existing body cavity or in other locations. Although isotopes can be used in some of the procedures of the invention, in some, the radiation is emitted from an electronic switchable x-ray source that can be modulated as to dose depth, via voltage in the x-ray source, and preferably also as to intensity, via current in the x-ray source. In a preferred form the source is a miniature x-ray tube, having a diameter on the order of roughly about ½-3 mm, and a length of about 5-15 mm.  
         [0008]     Pursuant to the invention a miniature x-ray tube is inserted into a balloon catheter, either before or after the balloon has been placed at the desired location in the patient. The x-ray source is switched on via a control unit outside the patient only when the balloon has been inserted, inflated and confirmed as to position, and with the patient and physician ready to administer the prescribed dose profile to the patient. Radiation dose delivery can be high compared to prior practice, about 5 to 50 Gy/hour. The x-ray source can operate in the range of about 40 kVp to 80 kVp.  
         [0009]     In another aspect of the invention, either a switchable x-ray source or an isotope can be used in a therapeutic radiation treatment procedure. The balloon of the catheter is doped with contrast medium, in or on the skin of the balloon. The inflation medium for the balloon, which may be a saline solution, need not have any contrast medium added. The balloon catheter is placed in a cavity of living tissue, i.e. in a patient, and the balloon is inflated and then verified as to position in the cavity. This can be done by an x-ray taken exteriorly to the patient, since the balloon skin with contrast medium will have its outline visible by x-ray, after which the position of the balloon can be adjusted, if necessary. Once the correct balloon position has been verified by external imaging, the x-ray source, which may be an isotope source or a switchable source, is placed in the balloon catheter (if a switchable tube the source can be placed in the balloon before insertion). The source preferably is moved through a series of positions within the balloon catheter to administer radiation to tissue adjacent to the balloon, in accordance with a prescribed dose profile.  
         [0010]     The use of a balloon catheter with contrast medium in or on the skin of the balloon, as opposed to being contained in a saline solution within the balloon, is a strong departure from the prior art. The advantage is that the physician will not over-dope the saline solution with contrast medium, thus maintaining the strength of the therapeutic radiation emitted from inside the balloon. The balloon wall has virtually no attenuating effect on the therapeutic radiation, when the radiation passes through the balloon in a normal or generally normal direction to the skin of the balloon. However, when the x-ray is taken from outside, the outline of the balloon will show up sharply because of the tangential direction of viewing that outline and the fact that the outline represents many times the wall thickness of the balloon, perhaps 20-40 times the density of contrast medium, thus contributing to the visible outline in the x-ray. 
     
    
     DESCRIPTION OF THE DRAWINGS  
       [0011]      FIG. 1  shows a catheter device of the invention with an inflatable balloon applicator within which is an x-ray source, shown at a cutaway of the balloon.  
         [0012]      FIG. 2  schematically shows the device of  FIG. 1  with the balloon inserted in a cavity of a patient&#39;s body and inflated.  
         [0013]      FIGS. 3 and 3 A are a schematic elevation showing the device in a patient&#39;s breast; and a graph indicating modulation of dose depth for x-rays from a switchable x-ray source for the situation of  FIG. 3  at different positions, in accordance with a dose prescription and taking into account adjacent organs and tissues.  
         [0014]      FIGS. 4 and 4 A are a schematic similar to  FIG. 3 ; and a graph showing an aspect of dose modulation, in this case modulation of dose intensity by modulating current in the x-ray tube, for different positions as shown in  FIG. 4 .  
         [0015]      FIGS. 5A, 5B  and  5 C show the catheter and the components of the catheter of the invention in greater detail.  
         [0016]      FIG. 6  schematically indicates the balloon of the catheter in cross section, as it is x-rayed from the exterior of a patient, with a graph indicating generally the attenuation of x-rays as a function of position on the balloon.  
         [0017]      FIG. 7  is a graph indicating path length for x-rays passing through the balloon as in  FIG. 7 . 
     
    
     DESCRIPTION OF PREFERRED EMBODIMENTS  
       [0018]     In the drawings,  FIG. 1  shows somewhat schematically an applicator  10  according to one embodiment of the invention, the applicator including a flexible control line or cable  12  leading from a controller, not shown, and a catheter or applicator portion  14 . A balloon  16  of the applicator and catheter is shown inflated in  FIG. 1 . The applicator device is generally as shown in co-pending application Ser. No. 10/683,885, filed Oct. 13, 2003.  
         [0019]     As shown, at the proximal end  18  of the applicator is a branch  20 . The three ports  22 ,  24  and  26  of this branch device may comprise a service port, a drainage port and a balloon inflation port, respectively. The functions of these ports are explained further below with reference to other drawings.  
         [0020]     A flexible main shaft  28  extends from the branch device  20  to the balloon  16 , and is sealed to the balloon at  30 . The balloon in  FIG. 1  is shown partially cut away to reveal an electronic x-ray source  32  within the balloon, at the end of the control line  12  and moveable longitudinally within the balloon  16  and catheter  10 . In preferred embodiments the x-ray tube  32  is less than 4 mm in diameter, preferably no greater than about 3 to 3.2 mm in diameter, and in some embodiments this tube is as small as 1 mm in diameter or even smaller.  
         [0021]     The shaft  28  is flexible, and may be highly flexible and pliable near the proximal end  18 , as explained in the co-pending application referenced above, for the purpose of folding the applicator over against the breast when not in use, when the control line  12  and x-ray source  32  are not inserted into the applicator, particularly for breast irradiation involving several dose fractions such that the applicator need not be removed between fractions.  
         [0022]     The flexible shaft provides a lumen for admitting a fluid to inflate the balloon  16 , while also providing a duct or lumen for insertion of the radiation source  12 , via guides connected to the balloon. The shaft  24  also preferably provides a channel for drainage of liquids from the body cavity within which the applicator is inserted. A drainage receptacle can be connected to the end of the drainage port or an aspirator can be used when needed to withdraw liquids. The applicator  10  is shown schematically in  FIGS. 2, 3  and  4  as inserted into a resection cavity of a breast for treatment.  
         [0023]      FIGS. 5A, 5B  and  5 C show the applicator  10  in greater detail, and with the balloon  16  deflated and collapsed. The service port  22 , in line with the flexible shaft  28 , as well as the drainage port  24  and the balloon inflation port  26 , are illustrated. Also shown is a distance scale preferably included, with distances shown at 6 cm, 7 cm, 8 cm, etc., up to about 15 cm, to indicate to the physician the total depth of the applicator into cavity and opening wound. This provides a direct and easily used means to determine the position of the distal end  35  of the applicator as it is being inserted. As shown in  FIGS. 5B and 5C , drainage is provided for the resection cavity via drain holes  36  at the distal end  35  of the applicator, beyond the balloon  16 , communicating internally to the drain port  24 , and also preferably via drain holes  38  shown just proximal of the balloon, for draining fluids which travel over the surface of the balloon. As in co-pending application Ser. No. 10/683,885, the balloon preferably has some form of liquid channeling means on its outer surface. This could be a multiplicity of bumps, allowing for liquid travel even though the balloon is engaged against the tissue, or a series of longitudinal ridges on the balloon surface to form channels. The drain holes  38  catch most of the liquid flowing in this manner, and these holes communicate with the drain port  24 .  
         [0024]     The balloon  16  may advantageously be formed of a silicone material, although other appropriate biocompatible materials can be used. The balloon material is bonded to the outside surface of the flexible shaft  28  in sealed relationship thereto, by known procedures.  
         [0025]      FIGS. 2, 3  and  4  indicate somewhat schematically the use of the applicator device  10  in a resection cavity of a human breast  41 , for radiation therapy. In  FIG. 2  the catheter  10  is shown with its balloon  16  shown in dashed lines, and the shaft  28  in the balloon forming a guide for an x-ray source which may either be a miniature x-ray tube or an isotope. A seal  40  is shown in  FIG. 2 , for sealing the flexible shaft  28  of the catheter/applicator against the surface of the skin where it enters the body. Also shown in  FIG. 2  is a connector  42  for connecting the applicator shaft, via the service port  22 , to an exterior cable  44  that contains the control cable  12 , leading to the controller (not shown) for the applicator and for the x-ray source, if the source is a controllable miniature tube.  
         [0026]      FIGS. 3 and 3 A illustrate the ability of the invention to achieve a more exact dose profile by use of a miniature electronic x-ray source in the applicator  10 , a source which is capable of voltage variation and thus variation of the depth of dose. As one rather simple example, four dwell positions are shown in  FIG. 3  and represented in a bar graph in  FIG. 3A . The deepest dwell position, position  1 , is closest to the lungs of the patient. Thus, the voltage is relatively low for this dwell position, controlling the depth of penetration into the surrounding tissue such that radiation will not reach the lungs to any appreciable degree.  
         [0027]     The second dwell position is farther from the lungs, and  FIG. 3A  shows that the voltage is increased for this dwell position, for a greater depth of penetration. Similarly, dwell positions  3  and  4  are progressively farther from the lungs and the voltage and depth of dose are progressively higher.  
         [0028]      FIGS. 4 and 4 A illustrate schematically the use of a switchable, controllable electronic x-ray source in the catheter  10 , wherein current is varied at different dwell positions in order to vary the dose intensity at different positions. In the schematic drawing of  FIG. 4 , four different dwell positions are again indicated for the electronic x-ray source, within the balloon  16  of the catheter  10 , the balloon positioned in a resection cavity in a patient&#39;s breast  41 . The control current does not vary the depth of penetration of the radiation, only the dose intensity. In the illustrated procedure, the current is varied in order to produce a uniform isodose profile. Thus, at positions  1  and  4  where the x-ray source is closest to tissue, the current is set at a lower level, while at dwell positions  2  and  3 , close to the center of the balloon  16  and of the resection cavity, where the tube is more distant from tissue, the current is set higher. Note that dose intensity can be controlled also by controlling the length of time the source is “on” at each dwell position, or simply by controlling the length of dwell at each position assuming the source remains “on”. These profiles of FIGS.  4  to  5 A are just examples of how the variation of voltage and current using an electronic x-ray source can be beneficially used accurately to create a required isodose profile.  
         [0029]      FIGS. 6 and 7  illustrate the balloon  16  having an x-ray contrast medium in or on the balloon wall. As explained above, this differs from prior practice in which a saline solution within the balloon contained a weak solution of contrast medium so that the balloon would show up in external x-ray imaging, for location of the balloon. In this case the contrast medium is only in or on the balloon wall, and this medium will absorb radiation, indicated at  46 , during external imaging; it will also absorb radiation from the therapeutic source and thus will attenuate the radiation delivered from inside the balloon to some extent. However, with a low concentration of such contrast medium in the balloon wall, the attenuating effect of the medium for radiation passing through the balloon at an angle normal or generally normal to the balloon wall will be small and essentially negligible. On the other hand, the effect of radiation, particularly x-ray radiation, passing tangentially through the edges of the balloon as indicated in  FIGS. 6 and 7 , will be at a maximum, since the radiation must pass through the balloon edge wise at this tangential angle, a much longer effective path length. The result is that a balloon  16  with such contrast medium can be located by external x-ray, visible in an x-ray image by its edges. This is demonstrated in  FIG. 7  showing effective path length of x-rays through balloon material as a function of distance from the center of the balloon. The densest outline of the balloon will be at its circumference, especially at distal and proximal ends of the balloon itself, where the wall material may be somewhat thicker at its attachment to the flexible shaft  28  and in any event, where the balloon has areas that are stretched far less due to the geometry of the balloon and its attachment to the flexible shaft  28  of the catheter device.  
         [0030]      FIG. 6  shows in a schematic approximation a graph of x-ray density (darkness or density of the line appearing in an x-ray image) on a vertical axis, versus position. For clarity the balloon  16  is represented directly adjacent to the graph, and showing the direction of x-ray radiation  46 . As illustrated, density is low in the x-ray image of the balloon at a region  48  in  FIG. 6  where the radiation passes generally normally through the balloon wall; however, spikes of extreme density are shown at  50  and  52 , where the rays must pass through considerable distance of the balloon wall on edge. As can be seen from the graph of  FIG. 7  (showing effective path length through both 4 and 5 cm diameter balloons), the effective path length at these tangent regions can be about 15 to 25 times greater than the normal path length. Thus, the contrast-doped balloon wall provides a far superior imaging arrangement than the prior saline solution, without adversely affecting therapeutic radiation.  
         [0031]     The procedures and apparatus described above are applicable to natural body cavities (e.g., bladder, uterus, vaginal), and naturally occurring lumens, as well as surgically created cavities. The term cavity in the claims is intended broadly to refer to natural or surgical cavities or lumens. Also, except where a switchable x-ray source is specifically called for herein for the advantages it offers in modulation or other purposes, the described procedures can ordinarily be performed using isotopes. The term brachytherapy device refers to either type of radiation source.  
         [0032]     The above described preferred embodiments are intended to illustrate the principles of the invention, but not to limit its scope. Other embodiments and variations to these preferred embodiments will be apparent to those skilled in the art and may be made without departing from the spirit and scope of the invention as defined in the following claims.