Patent Publication Number: US-7901345-B2

Title: Miniature X-ray unit

Description:
RELATED APPLICATION DATA 
     This application is a continuation of co-pending U.S. patent application Ser. No. 11/059,924, filed Feb. 17, 2005, which is a continuation of U.S. Ser. No. 10/360,502, filed Feb. 6, 2003, now U.S. Pat. No. 6,910,999, which is a continuation of U.S. Ser. No. 09/710,304 filed Nov. 10, 2000, now U.S. Pat. No. 6,540,655, the priority of which is claimed under 35 U.S.C. §120, and the contents of which are incorporated herein by reference in their entirety, as though set forth in full. 
    
    
     FIELD OF THE INVENTION 
     The invention relates to a miniaturized x-ray source situated in a catheter that generates x-rays while minimizing risk from exposure to the x-rays. 
     BACKGROUND OF THE INVENTION 
     Traditionally, x-rays have been used in the medical industry to view bone, tissue and teeth. X-rays have also been used to treat cancerous and precancerous conditions by exposing a patient to x-rays using an external x-ray source. Treatment of cancer with x-rays may cause well documented side effects, many of which are due to the broad exposure of the patient to the therapeutic x-rays. 
     To improve medical treatment and diagnosis of patients, minimally invasive endoscopic techniques have been developed and are used to treat a variety of conditions. Endoluminal procedures are procedures performed with an endoscope, a tubular device into the lumen of which may be inserted a variety of rigid or flexible tools to treat or diagnose a patient&#39;s condition. 
     The desire for improved minimally invasive medical devices and techniques have led to the development of miniaturized x-ray devices that may be used in the treatment or prevention of a variety of medical conditions. International Publication No. WO 98/48899 discloses a miniature x-ray unit having an anode and cathode separated by a vacuum gap positioned inside a metal housing. The anode includes a base portion and a projecting portion. The x-ray unit is insulated and connected to a coaxial cable which, in turn, is connected to the power source. An x-ray window surrounds the projecting portion of the anode and the cathode so that the x-rays can exit the unit. The x-ray unit is sized for intra-vascular insertion, and may be used, inter alia, in vascular brachytherapy of coronary arteries, particularly after balloon angioplasty. 
     International Publication No. WO 97/07740 discloses an x-ray catheter having a catheter shaft with an x-ray unit attached to the distal end of the catheter shaft. The x-ray unit comprises an anode and a cathode coupled to an insulator to define a vacuum chamber. The x-ray unit is coupled to a voltage source via a coaxial cable. The x-ray unit can have a diameter of less than 4 mm and a length of less than about 15 mm, and can be used in conjunction with coronary angioplasty to prevent restenosis. 
     Miniaturized x-rays are not foolproof, however, and still present difficulties upon use. The x-ray unit generates heat, which can damage adjacent healthy tissue. Additionally, the x-rays are not localized and irradiate local tissue rather than only irradiating the desired tissue. It is difficult to maintain the positioning of these instruments at the desired location. Improved miniaturized x-ray units that overcome these difficulties are desirable. 
     Other techniques are used to treat tumors with radiation, including planting a seed of radioactive material at the tumor site, a procedure that is typically accomplished with endoluminal procedures. However, the patient becomes “hot”, i.e., radioactive, and the procedure risks exposure of the medical personnel to radiation. 
     As noted above, many types of cancerous and precancerous conditions are treated by externally irradiating the tumor or site with x-rays. However, the x-rays are broadcast over a large area of healthy tissue in addition to the tumor because the radiation is administered from outside the body so that it penetrates the skin and any internal organs or tissue to reach the desired site. To avoid this, miniaturized x-ray systems which generate x-rays at the desired site are a desirable alternative to conventional apparatus. 
     Since many types of cancer occur in a body cavity or lumen, such as in the rectum, vagina, esophagus or pulmonary passages, it would be desirable to treat these cancers using miniaturized x-ray sources in combination with endoscopic techniques, which are minimally invasive to the patient, so that the cancer or other intraluminal tissue is directly treated with x-rays. This technique would minimize exposure of healthy tissues to the x-rays. 
     The present invention overcomes the difficulties associated with x-ray therapy and apparatus of the prior art by providing an endoscopic x-ray device that generates x-rays at the site of treatment and minimizes exposure of other tissues to irradiation. 
     SUMMARY OF THE INVENTION 
     A miniaturized x-ray apparatus for delivering x-rays to a selected site within a body cavity includes a catheter having at least one lumen and an x-ray transparent window at a distal end thereof; an x-ray source in the lumen adjacent said x-ray transparent window; a movable x-ray shield positioned to direct x-rays from the source through the x-ray transparent window to the selected site. The x-ray device ranges from 2 mm to about 15 mm. 
     The x-ray source is positioned inside an x-ray shielded catheter lumen, i.e., the catheter lumen is impenetrable by x-rays except in the area of the x-ray transparent window which is described in more detail below. 
     The x-ray source includes a cathode and an anode and an insulating material. The anode and cathode are separated by a vacuum gap. Insulating material may surround the base anode and cathode. 
     Preferably, a separate lumen of the catheter includes a camera through which medical personnel may observe the body lumen and procedure. 
     In a preferred embodiment, inflatable (anchoring or positioning) balloons are provided on the exterior of the endoscope to maintain the desired position of the instrument once inserted into the lumen. These balloons may be filled with a gas via catheter lumens connected to a gas or fluid source. Preferably, the balloons are filled with a fluid that absorbs x-rays so that the fluid will help prevent irradiation of undesired tissue. The gas and or fluid will also preferably help to absorb heat generated during the procedure to prevent burning of local tissue. A thermocouple may be positioned on the exterior of the endoscope to monitor the temperature at the treatment site. 
     In an alternative embodiment, the catheter includes an x-ray source and the anchoring balloons which are inflatable with gas or fluid as described above. This embodiment does not include a shield. 
     Another alternative embodiment provides a catheter having a miniaturized x-ray device and a stationary x-ray shield having an x-ray transparent window. 
     The invention is described in further detail hereinbelow. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a is a miniaturized x-ray device according to the prior art. 
         FIG. 2  is the x-ray emission pattern from the device in  FIG. 1 . 
         FIG. 3  is a longitudinal cross section of a miniaturized x-ray device of the present invention. 
         FIGS. 4   a  and  4   b  are axial cross-sections of the device of  FIG. 3  showing the rotational motion of the x-ray shield about a central axis. 
         FIG. 5  is a cross-section of a catheter having circulation lumens to inflate positioning and/or anchoring balloons. 
         FIG. 6  is the catheter of  FIG. 5  showing inflated positioning and/or anchoring balloons. 
         FIG. 7  is a miniature x-ray device having both positioning and anchoring balloons. 
         FIG. 8  is an embodiment of a miniature x-ray device having a multi-chambered balloon filled with coolant and having a thermocouple. 
         FIG. 9  is a preferred embodiment of a miniature x-ray device having a laser positioning system according to the invention. 
         FIG. 10  is a cross section of a miniature x-ray device having a laser positioning system showing operation of the laser and x-ray shutters. 
         FIG. 11  is a preferred embodiment of a miniature x-ray catheter x-ray having an x-ray source located inside a catheter having an x-ray transparent window and a balloon positioning system. 
     
    
    
     DETAILED DESCRIPTION 
       FIG. 3  is a longitudinal cross section of a preferred x-ray apparatus according to the invention, inserted through the working channel of a endoscope (not shown) in a bodily lumen at a tumor site. The device  1  includes an x-ray source  10  which is connected to power supply  12  by electrically conductive cable  13 , e.g. a coaxial cable. X-ray source  10  includes a vacuum tube which maintains vacuum conditions therein and houses the electrodes of the x-ray source. Power supply  12  delivers sufficient energy to x-ray source  10  to generate therapeutically effective x-rays. Typically, voltages of from 10 to 60 kilovolts (kV) are needed to generate x-rays from x-ray source  10 . X-ray source  10  is located inside the lumen of x-ray tube  16  which is made of a material substantially or completely impenetrable to x-rays like lead or steel, except where x-ray transparent window  18  is positioned so that x-rays may exit the device and reach the desired site. Window  18  may circumferentially extend about the entire circumference of the x-ray tube  16 , or may only be extend partially about the circumference of the x-ray tube. 
     Suitable materials for the window include beryllium, glass, ceramic, plastic, mica. Additional coatings of metal or insulating material may be layered or coated on the window material as needed. 
     X-ray shield  15  is made of a material that is impenetrable to x-rays located in the catheter lumen and is rotatably connected to an external controller such that it may be rotated about a central axis to block x-rays from reaching non-selected tissue as shown in  FIGS. 4   a  and  4   b . X-ray shield  15  may be connected to a rotatable knob located at the proximal end of apparatus  1  so that x-ray shield  15  may be manually or otherwise adjusted to the desired location, which is typically opposite the site of treatment. 
     Device  1  preferably includes separate lumen for receiving a miniaturized camera, that may be retractably inserted into the body lumen. The camera is connected to a viewing screen so that the physician can view the position of the device in the body lumen. 
     An important advantage of a device embodied above compared to apparatus of the prior art is easily discerned by comparing the device of  FIG. 3  with the prior art apparatus of  FIG. 1 . As shown in  FIG. 2 , the x-ray pattern of the prior art device extends circumferentially from the location of the x-ray source in an unidirectional manner so that selected and non-selected tissue is irradiated. The x-ray shield of the subject apparatus limits allows medical personnel to limit radiation exposure to substantially only selected tissue, reducing exposure of healthy tissue to x-rays. 
     A preferred embodiment, shown in  FIGS. 5 ,  6  and  7  includes at least one inflatable positioning balloon  20  adhered to the outer wall of the x-ray tube. Positioning balloon  20  communicates with a gas or liquid reservoir via a duct and is inflated after proper positioning of the apparatus in the body lumen so that the position of the x-ray source is maintained throughout treatment. Positioning balloon  20  may be adhered to the exterior wall of the x-ray tube by a suitable adhesive. Alternatively, the balloons are positioned in compartments located inside a lumen of the device or in recesses provided in x-ray tube  16  so that they are not exposed until needed. It is preferred that a plurality of balloons are provided. Alternatively, a multi-chambered balloon  21  is provided to aid proper positioning of the apparatus in the body lumen as shown in  FIG. 8 . 
     In a particularly preferred embodiment, a gas or liquid coolant is passed through balloon  20  via circulation lumens which communicate with the interior of positioning balloon  20  and are connected to a gas or liquid reservoir. A respective circulation duct is provided for each balloon or balloon chamber so that they may be independently inflated. The positioning balloons  20  may be inflated with a gas or a liquid, but an x-ray absorbent liquid is preferred. Normal saline is a particularly preferred liquid because it has a high heat capacity, is x-ray absorbent, and, in the unlikely event of leakage, is biocompatible with the patient. 
     Optionally, anchoring balloons  22  may be positioned proximal and distal to positioning balloon  20  to steadfastly anchor the apparatus in the desired site by fully inflating the anchor balloons, and finer positioning adjustments may be made with positioning balloons  20  which are placed nearly adjacent the x-ray source. In a particularly preferred embodiment, anchoring balloons  20  are positioned proximal and distal to the x-ray window to anchor the endoscopic device at the desired site. 
     Thermocouple  26  may be optionally affixed or placed in the vicinity of the x-ray source to measure temperature during the procedure. Thermocouple  26  may be in the form of a bimetallic strip and is operatively connected to a temperature display device so that the temperature is monitored during the procedure. 
     Apparatus preferably includes a camera catheter  24  to view inside the body cavity so that the endoscope can be properly positioned at the desired site. The guide may be positioned in the same tube as the x-ray source or may be positioned in a tube parallel to the x-ray source  7 . 
     In a particularly preferred embodiment shown in  FIGS. 9 and 10  a light source  30  is provided in the x-ray catheter and is used to position the device such that substantially only the desired site is irradiated. Light source  30  is preferably a laser, but other types of illuminating devices may also be used. Light source  30  is positioned inside the catheter lumen in the vicinity of x-ray source  10 , but is a sufficient distance from the source so that the light source is not damaged during operation. Alternatively, light source  30  may be separated from x-ray source  10  by a suitable insulating material. Light source  30  is operatively connected to a power source. 
     Laser shutter  32  and x-ray shutter  33  are positioned one above the other and are independently opened and closed via an operable connection with respective manual opening devices. In a preferred embodiment, x-ray shutter  33  is automatically opened by an opening means when the x-ray is activated so that it is only open during periods of operation of the x-ray source, and closes when the x-ray source is not activated. The shutters operate in a known manner and are formed by a plurality of retractable portions ( 32   a  and  32   b ; and  33   a  and  33   b ) which operate in conjunction with their respective counterpart to form an aperture through which light and x-ray may pass. 
     In operation, the selected site is illuminated as shown in  FIG. 9  with light source  33 , and the field of illumination substantially corresponds with the field of irradiation. Thus, by simply illuminating the site of operation and viewing with the camera, it is possible to determine the site of radiation prior to irradiation with the x-ray. Then the anchor and positioning balloons can be properly adjusted, and the site can be irradiated with the dose of x-ray. 
       FIG. 11  is an embodiment of a miniaturized x-ray device  100  having an x-ray source  101  attached to electrically conductive cable  102  which has an inflatable balloons  20  adhered to an outer surface thereof. The balloons communicate with a fluid or gas source as described above to aid positioning of the x-ray source at the desired site. 
     The present invention also relates to methods of treatment, prophylaxis and adjunctive therapy using the miniaturized x-ray apparatus of the present invention. Suitable for use with other endoscopic equipment, the x-ray device is of an appropriate size such that it may be used to treat cancers of bodily lumens such as colorectal cancer, vaginal cancer, esophageal cancer, pulmonary cancers such as lung cancers, stomach cancer, oral cancers, or any cancer accessible by a bodily lumen by positioning the device adjacent the target tissue and irradiating the tissue with a therapeutically effective amount of x-rays. In similar fashion, one can treat pre-cancerous conditions or conditions related with cancer such as gastroesophageal reflux disease (GERD). Preferably, the selected site is illuminated prior to irradiation such that field of irradiated tissue is determined prior to irradiation of the site. 
     The apparatus of the invention may be used in conjunction with imaging devices such as visual, x-ray, magnetic or ultrasound to aid in positioning of the device inside a body lumen. 
     Although the present invention has been shown and described with respect to several preferred embodiments thereof, additional embodiments will be apparent to the skilled artisan without departing from the spirit and scope of the invention. 
     All cited references are incorporated herein by reference.