Abstract:
Treatment of lesions in any luminal or organ system of mammalian anatomy is performed using an electronic source of ionizing radiation and aided by an endoscopic or percutaneous approach.

Description:
BACKGROUND OF THE INVENTION 
       [0001]    This invention is concerned with therapeutic irradiation of lesions in organs or lumina of mammalian patients, especially humans. 
         [0002]    Therapeutic delivery of radiation therapy to many organs, lumina, and systems within the body using radioactive isotopes is well known. Presently, radiation therapy is directed to tissue within an organ system of the body that permits the introduction of the device to both target and treat; examples of routes that could be used are the gastrointestinal tract and all its tributaries, i.e. the common duct hepatic duct and the pancreatic duct, the urinary tract and its tributaries, i.e. the urethra and ureter providing access to the kidney and all distal organ systems of the urinary tract, the vascular system including the lymphatic system, which will provide access to any organ system in the body including the integument, the neurological, the endocrine, the pulmonary, the musculoskeletal and the hematopoietic systems. This list should not be considered complete because of other points of access to all areas of the body via a percutaneous or transvisceral route specific portions of the alimentary, biliary, vascular, neurological, gynecologic, and urinary systems. Traditionally, therapeutic radiation is generated by large units operating outside the patient and is a beam of radiation directed to specific anatomy. If the beam is omni directional, shielding of non-diseased areas adjacent to the anatomy to be treated is required. In order to avoid damaging exposure to areas of the patient&#39;s skin and other tissue leading to the target region, multiple beams of radiation may be directionally administered so as to intersect at the lesion or abnormality being treated. These beams may be applied simultaneously or sequentially, such that the prescribed dose is applied to the tumor, but lesser radiation is applied to normal tissue. Irradiation using such intersecting, externally-applied beams is sometimes known as intensity modulated radiation therapy, or IMRT. 
         [0003]    In some instances, radioisotopes are used within organs and lumina within the body in an effort to more directly treat diseased tissue. Because of the isotropic nature of the radiation emitted by radioisotopes, however, present methods of internal treatment may require the therapist to compromise in preparing treatment plans in order to prevent damage to normal tissue adjacent to the target lesions, but still effectively treat the lesion. The potential for serious complications exists. Thus, treatment of the abnormalities is often times compromised resulting in less than optimal therapy to the tumor itself. In addition, use of radioisotopes has attendant radiation safety concerns for therapeutic personnel. The practical effect of these limitations and concerns is that both externally and internally applied treatment modalities lack optimal targeting specificity, and are less focused on the tumor than desired. As a consequence, normal tissue is damaged. 
         [0004]    In view of the shortcomings of the methods described above, there is a need for apparatus and methodology for delivery of a controllable, more finely focused radiation therapy. It is therefore an object of this invention to enable the therapist the ability to accurately direct the radiation therapy at the lesion according to an optimal plan, either by manual control of the radiation source, aided by direct visualization of the target area during the treatment process, or by using automated control methods. It is a further object of this invention that radiation risk to both the therapist and the patient be minimized during the treatment process. 
       SUMMARY OF THE INVENTION 
       [0005]    Small electronic x-ray radiation sources are known (for example those disclosed in U.S. Pat. No. 6,319,188, the specification of which is incorporated herein in its entirety by reference) and along with their methods of use, comprise a part of this invention. Using an electronic radiation source, penetration depth can be controlled and the therapeutic radiation field can be limited or shaped. With control of the radiation beam as described below and, with this invention, direct visualization or imaging assures that the target lesion is treated while essentially avoiding injury to normal tissue or structure adjacent to the lesion. If desired, the control of radiation exposure to normal tissue within or adjacent to the operative site can be provided by methods other than by visualization, for example by endoscopically positioned radiation shielding. See, for example, copending application Ser. No. 11/471,277, the disclosure of which is incorporated herein by reference. Unlike the typical isotope radiation used therapeutically, electronically generated, low intensity x-ray radiation is effectively attenuated by positioning even modest shielding material over the areas to be protected. 
         [0006]    Both rigid and flexible catheter, laparoscopic, and endoscopic apparatus and methods of use exist which comprise fiber optic or other methods to illuminate the operative field and coherent fiber optic bundle or camera means wherein the therapist is able to view his field, either by looking through a lens or by observing his field on a monitor driven by inputs from within the patient. Since such catheters and endoscopes often comprise fiber optic bundles, it is a simple matter using conventional methods to assign optic channels for visual light markers directed at the point of incidence of the x-rays onto tissue. For example, this marker might comprise an “X” at the point of incidence. With such markers, the surgeon can visually aim his beam at the target tissues for which treatment is prescribed. 
         [0007]    Many such endoscopes or laparoscopes additionally include operating channels through which instruments can pass into the operative field. Through such an endoscope operating channel, an instrument can be both accurately aimed and manipulated or actuated under direct or monitored visualization by manipulating the endoscope. Such an instrument might comprise a wand or catheter with an electronic radiation source at or near its distal extremity, and which may easily pass through the working channel or an auxiliary entry port. If desired, such a radiation source can have a narrowly directed beam. The shaft of the instrument can also comprise lumina for flushing and suctioning the operative site. As an alternative to flushing and suction functionality in the endoscope, the catheter itself may be fashioned with lumina to provide such functionality. 
         [0008]    Some visualization means currently used in minimally-invasive surgery comprise a semiconductor chip camera (CCD or CMOS device) which is very small, and which can communicate outside the patient&#39;s body for visualization of the field by either wire or wireless means. Such a camera, along with illumination and other optional features including those mentioned above, can all be incorporated into a radiation source catheter, thus integrating the functions of the endoscope and the radio-therapy catheter into one device. Such integration can result in a smaller device than a conventional endoscope adequate to accommodate a source catheter and its associated systems. 
         [0009]    Armed with one of the devices as described above, a minimally-invasive radiation therapist can gain access to any lesion which is within an organ system of the body that permits the introduction of the device to both target and treat the lesion or other abnormality. Examples of access routes that can be used comprise the gastrointestinal tract and all its tributaries, i.e. the common duct, hepatic duct and the pancreatic duct, the urinary tract and its tributaries, i.e. the urethra and ureter providing access to the kidney and all distal organ systems of the urinary tract, the vascular system including the lymphatic system, which will provide access to any organ system in the body including the integument, the neurological, the endocrine, the pulmonary, the musculoskeletal and the hematopoietic systems. In addition, known methods of percutaneous or transvisceral access can be utilized, either through natural anatomic entrances into body, or by percutaneous access using known methods. A planned dose of therapeutic radiation can therefore be delivered accurately to any abnormality amenable to radiation as a form of curative or palliative treatment. Since the radiation field is controllable, and since risk of inadvertent radiation exposure to the patient and therapeutic personnel can be easily minimized, safe and controlled targeting of tissue under direct vision is possible with minimal protective measures. 
         [0010]    The invention is applicable with endoscopes, laparoscopes, catheters and similar access devices, although the word endoscope is primarily used in the following description. The word endoscope is to be understood as including any such shaft device for extending deeply into a patient&#39;s anatomy, percutaneously or through a natural anatomical entrance, and with viewing or placement-confirmation capability. 
     
     
       DESCRIPTION OF THE DRAWINGS 
         [0011]      FIG. 1  shows a system of the invention schematically in relation to a patient. 
           [0012]      FIG. 2  is a side view of a catheter with a miniature x-ray source at it distal tip. 
           [0013]      FIG. 3   a  is a side view of an integrated embodiment of the invention comprising an x-ray source, imaging, targeting, flush and suction functionality, steer-ability, and illumination in one device. 
           [0014]      FIG. 3   b  is a cross-sectional view through the shaft of the embodiment of  FIG. 3   a.    
           [0015]      FIG. 3   c  is a partially sectioned side view of the tip of the embodiment of  FIG. 3   a.    
           [0016]      FIG. 3   d  is a distal end view of the tip of the embodiment of  FIG. 3   a.    
       
    
    
     DESCRIPTION OF PREFERRED EMBODIMENTS 
       [0017]      FIG. 1  shows a system  100  comprising an endoscope  101  with a flexible shaft  102 , and having at its distal tip, provision for lighting the operative field  200  and the tumor  201 . Light is provided by light source  506 . The endoscope  101  also comprises imaging apparatus and transmission means to enable viewing of the operative field  200  and the tumor  201  on a monitor  301  (tumor shown as  201 ′). Note the target “X”  202 ′ superimposed on tumor image  201 ′, and source  502 ′ on field image  200 ′. An image transmission means  104  can be by a conductor or conductors, coherent fiber optic bundle, or by wireless transmission to a processor  303 , of which the monitor  301  is a part. A camera can be located at the distal end, as discussed below. A keyboard, tablet, voice activated or other input device  302  completes processor system  300 . 
         [0018]    Within the endoscope  101  is a radiation source catheter  501 , having a miniature x-ray tube  502  at its distal tip and a hub  503  at its proximal end. The power supply  400  provides power to drive the x-ray tube  502  through a power connection cable  401 . The radiation source  502  has a distally directed radiation beam  105 , such that radiation beam can be directed onto tumor  201  by manipulating the distal tip of endoscope  101  within the operating field. Alternatively, the beam can be directed elsewhere. At the proximal end of the catheter  501  is the catheter hub  503 . The hub comprises a connection to the power cable  401  coming from the power supply  400  to drive the x-ray tube, a connection to the on/off switch  504 , and an optional suction, flush or vent system  505  connection communicating with the distal tip of the catheter  501 , as described above. 
         [0019]    The endoscope  100  generally has a flexible section which can be steered as desired by the therapist. The endoscope has a hub  103  at its proximal end, the controls of which can be used to manipulate the direction in which the distal tip is directed, and hence the catheter tip and/or visualization apparatus. Such controls are well understood by those of skill in the art, and are therefore not detailed here. By hand manipulation of the endoscope, the lesion can be illuminated and targeted, and by advancing or withdrawing the catheter  501 , the distance from the radiation source  502  to the lesion  201  can be optimized for therapeutic effect. Because visualization methods such as those described often lack the means to provide depth perception, the catheter may be advanced to touch a visualized surface within the operative field, then withdrawn a calculated distance for free beam targeting at optimal range. Graduated marks  106  can be provided on the catheter shaft at or about the endoscope hub  103  to facilitate this procedure. 
         [0020]    The input device (keyboard, tablet or voice-actuated device)  302  is used to input prescription dose parameters for the x-ray source  502  into the processor  303 . The processor  303  computes input voltage and current (and if required, laser light) parameters corresponding to the prescription, and commands the power source  400  as necessary to produce the prescribed dose. During therapy, a manual switch  504  emanating from the catheter hub  503  is used to control whether the source  502  is powered and active. Preferably, the switch  504  is normally open (switching radiation off when untended) such that radiation is only emitted while the therapist manually closes the switch. If desired, the source catheter  501  or endoscope  101  may include a lumen or lumina connected to a circuit  505  connected to a suitable receptacle (not shown) to vent, flush or suction the operative field. 
         [0021]    If a greater degree of automation is desired, the apparatus and system may further comprise optical recognition methodology as described in co-pending patent application Ser. No. 60/742,118 filed Dec. 2, 2005, the specification of which is included by reference herein in its entirety. The processor system may then optionally comprise a timer and audible signaling device, for example a buzzer, to indicate to the therapist when the prescribed dose has been delivered. This is accomplished by cumulatively tracking delivered dose intensity over time. By comparing the real-time cumulative dose with a prescribed treatment plan and prescription dose information entered into the processor, verification of treatment to prescription can be accomplished and radiation emission may then be terminated. This system eliminates treatment beyond defined lesion boundaries as determined by the therapist, and can further modulate dose intensity within the treatment area. 
         [0022]      FIG. 2  shows a catheter  501  incorporating a miniature radiation source  502  at its distal tip. Miniature x-ray sources are described in U.S. Pat. No. 6,319,188, but in general consist of a flexible, high-voltage cable connected to a power source and controller at its proximal end and to the small x-ray tube at its distal end. The x-ray tube has a cathode (not shown) preferably at its proximal end, which can be caused to emit electrons (for example by heat) and a target anode (not shown) at its distal end. The voltage between the cathode and anode causes acceleration of the electrons emitted by the cathode past the anode, where they next impinge on the target, resulting in bremsstrahlung, or in this case, the creation of x-rays. The spectrum of energies produced is related to the voltage applied between the cathode and anode and the target material used. It is this variable voltage that can be used to control the penetration depth into tissue of the emitted X rays. 
         [0023]      FIGS. 3   a  through  3   d  depict a single device with all functionalities described above combined into one device embodiment. Other functionality could be included or substituted. Device  600  shown in  FIG. 3   a , which can be called an endoscope with onboard x-ray source, comprises a shaft  601  having a central lumen for a source catheter  615  having an x-ray source  605  at its distal tip. The source  605  is positioned at or near the distal end of the shaft  601 . At the proximal end of the shaft  601  is a conventional hub  602 , comprising a central port  610  to accommodate the source catheter  615  ( FIG. 3   c ) and the necessary sub-systems  402  to support operation of the source  605 . These systems may include filament current or laser energy to activate the cathode, accelerating voltage, and fluid flow for cooling. A lower auxiliary port  508  is provided for flushing and suction, and an upper port  507  for light input for illumination and targeting. Just proximal of hub  602  is a sort of swash plate  608  for manipulating the wires  609  (of which there are at least two for planar manipulation or three for spatial manipulation) for bending the flexible section or sections of the shaft  601 , i.e. bonding the endoscope. The wires act in a coordinated, push-pull manner. These wires  609  pass through lumina in the shaft  601  (see  FIG. 3   b ) but are anchored at their distal ends which are positioned at the distal extreme of the flexible shaft portion  616  of the shaft  601  in  FIG. 3   c .  FIG. 3   b  shows the lumina  610  for the wires  609 , as well as lumina  612  for flushing and suction. These fluid lumina  612  terminate proximally in the port  508  where they are connected conventionally to fluid source and evacuation systems in the operating room. Lumina  612  terminate at ports  603  (see  FIGS. 3   a ,  3   c ) near the distal tip of shaft  601 .  FIG. 3   b  also shows lumina  611  for fiber optic bundles for illumination, and optionally for targeting. Proximally, these lumina  611  terminate in port  507  where they are conventionally connected to a light source or sources, such as is shown in  FIG. 1  as light source  506 . Distally, these fibers terminate at the end of the shaft  601  and provide an illumination cone  606  (solid line cone in  FIG. 3   d ). 
         [0024]    Targeting is accomplished by edge fibers  613  positioned at the circumferential extremes of lumina  611 . (See  FIGS. 3   b ,  3   d .) These fibers  613  transmit colored light which preferably contrasts with the operative field (for example, green light). Their distal ends are beveled or otherwise shaped so as to provide a useful, visible target  202 , locating the direction of emitted x-rays for the therapist. (Note the “X” shaped image  202 ′ on the monitor screen in  FIG. 1 ). The target shape is arbitrary. 
         [0025]    Adjacent to the source  605  at the distal tip of shaft  601  are two chip cameras  604  in diametrically opposed positions. With this arrangement, stereoscopic visualization is provided through a visualization cone  607  (phantom line cone in  FIG. 3   d ). Alternatively, one camera, or a coherent fiber bundle can be substituted for these cameras  604 . Such a coherent bundle could pass through the shaft  601  through lumina  611 . 
         [0026]    Although the above describes a source-bearing catheter positioned in a lumen of an endoscope or device, the construction can be otherwise and more integral. With the x-ray source  605  at the distal end of the device, the shaft  601  can be constructed in various ways, so long as the source  605  is supported by adequate dielectric and standoff spacing for high-voltage conductors leading through the shaft. The dielectric material can be formed solidly and fixedly in the center of the endoscope  600 . The entire shaft  601  or endoscope  600  could be of dielectric material, with conductors adequately spaced and not necessarily in the central space described as a lumen with catheter  615  in  FIGS. 3   a - 3   d.    
         [0027]    The miniature electronic x-ray source  502 ,  605  described in connection with an endoscope has great advantages over treatment with isotope radiation. 
         [0028]    Radiation from radioisotopes is emitted in a known manner with a decaying intensity measured by the isotope&#39;s half-life—the time at which half the original intensity remains. Within practical time constraints, these parameters for a given radioisotope are fixed and they cannot be altered thus offering no possibilities for control. Furthermore, radioisotopes emit radiation at a few distinct energy bands, radiation from each band having its own ability to penetrate tissue and deliver dose. For example, the high-energy band of radiation emitted from  192 Ir, the most common high dose-rate brachytherapy isotope, penetrates through large thicknesses of shielding materials. In addition, isotopes are always “on”, so controlling the output with on/off switching is not possible. Other common medically relevant radioisotopes also have emission spectra containing high energy components that make selective shielding within a body cavity impractical due to space considerations. The radiation from these isotopes will penetrate any practical thickness of shielding material. This high-energy radiation easily penetrates well beyond the target site requiring therapy, thus delivering radiation to healthy parts of the body and risks injury. 
         [0029]    In contrast, with electronically controlled radiation sources, the shape of the anode and its structure, and any minimal shielding utilized, determines the directionality of the x-rays emitted. The emitted x-rays may be emitted isotropically, they may be directed radially, axially, or a combination thereof. Anode shaping is well known by those skilled in the art of x-ray generation apparatus. Anode shape, target thickness and target configuration can be used to change the radiation profile emitted from the miniature x-ray source. For low energy miniature x-ray sources, thin radiation shields can easily produce directional radiation. For electronically produced x-rays, the acceleration voltage determines the energy spectrum of the resulting x-rays. The penetration of the x-rays in tissue is directly related to the energy of the x-rays. The cumulative radiation dose directed at a point of the lesion may be controlled by x-ray source beam current or “on” time within the body of the patient. 
         [0030]    In using the system of the preferred embodiment, the therapist enters the desired prescription dose into the processor system  300 . The processor computes power parameters and transmits those to the power supply  400 . The therapist then positions the endoscope  100  within the anatomical cavity in which the treatment is to take place, and if necessary, performs flushing and/or suctioning to prepare the treatment field. This can be done under direct visualization. Next, and if needed, the therapist can verify calibration of the radiation source using an ion chamber or similar device. Then, the radiation catheter  501  is introduced and positioned to treat the lesion, both by use of the endoscope controls and by advancing the catheter  501  to achieve the proper treatment range between the tip of the source and the lesion. When ready to proceed with the treatment, the therapist closes the switch  504 , continually or intermittently as desired, until the processor alarm sounds (or total time is determined by other means) at which point the switch  504  is opened (released), concluding the treatment. As previously described, some of these steps may be wholly or partially automated. 
         [0031]    Although this embodiment is discussed with particular reference to endoscopic practice, similar methods can be utilized with either laparoscopic or catheter methods without departing from the scope of the invention. References to endoscope or endoscopic in the claims is to be taken as referring to any of those instruments and methods. 
         [0032]    The above-described preferred embodiments are intended to illustrate the invention, but not to limit its scope. Other embodiments and variations to these preferred embodiments will be apparent to those of skill in the art and may be made without departing from the spirit and scope of the invention.