Patent Number: 
Section: description

The present invention provides a flexible catheter having at its tip a miniature transformer coupled to an x-ray generator for powering the x-ray generator. The x-ray generator and the transformer can be formed as a monolithic device, or alternatively, they can be formed as separate devices that are mechanically and electrically coupled to one another. The x-ray generator produces x-ray radiation in a biologically effective wavelength range, for example, in a range of about 10 keV to about 40 keV. Further, the transformer includes a primary winding that receives an input AC voltage having a root-mean-square amplitude in a range of about 100 V to 4 kV, and a secondary winding that up-converts the input voltage to generate an output voltage having an rms amplitude in a range of about 10 kV to about 40 kV for powering the x-ray generator. The use of the transformer in proximity of the x-ray generator, and more preferably, as a portion of a monolithic x-ray generation unit formed of the transformer and the x-ray generator, advantageously allows a more flexible electrical cable to be utilized for transmission of an input voltage across the catheter, and also allows a safer operation of the catheter, as described in more detail below. With reference to FIG. 1, an exemplary catheter 10 according to the present invention includes a flexible body 12 having a lumen 14 that extends from a proximal end 16 of the flexible body to a distal end 18 thereof. The flexible body has an outer diameter in range of about 1 to about 4 millimeters, and is sufficiently flexible to be readily guided through a patient""s lumen, e.g., a patient""s artery, to be deployed in proximity of a target region that needs to be treated with x-ray radiation. A variety of materials can be employed for manufacturing the flexible body 12. These materials can include, but are not limited to, polyethylene and Teflon(trademark). An x-ray generator unit 20 is coupled to the catheter""s body in a distal end region thereof, and more preferably, at the tip of the catheter by one or more support elements 22. The exemplary x-ray generator unit 20 includes an x-ray generator 24, and a transformer 26 that provides power for the x-ray generator 24. In this embodiment, the x-ray generator 24 and the transformer 26 are formed as a monolithic device, as discussed in detail below. In other embodiments, the x-ray generator 24 and the transformer 26 can be formed separately and be mechanically and electrically coupled to one another. A flexible electrical cable 28 extends from the proximal end 16 of the catheter body 12 to its distal end 18, and is electrically coupled to the transformer 26. The electrical cable 28 can be, for example, a flexible coaxial cable that is connected at one end, via a connector 30 and a cable 32, to a power supply 34. As shown in FIG. 2, the coaxial cable 28 can include an inner conductor 36, and an inner insulation layer 38 having a thickness in a range of about 0.01 mm to 0.2 mm that covers the inner conductor 36. The exemplary coaxial cable 28 further includes an outer conductor 40, for example, in the form of braided copper wiring, that is covered by an outer insulation layer 42 having a thickness in a range of about 0.001 mm to about 0.2 mm. In operation, the outer conductor 40 is grounded, and the inner conductor 36 is coupled to a primary winding of the transformer 26, as described in more detail below, to transmit an input AC voltage from the power supply 34 to the primary winding. The input AC voltage can have a root means square (rms) amplitude in a range of about 100 V to about 4 kV, and a frequency in a range of about 60 Hz to about 10 MHz. Although in this embodiment, the catheter 10 includes a lumen, in another embodiment, the flexible body of the catheter can be constructed without a lumen, and the x-ray generator unit 20 still be coupled to the distal region of the catheter. Alternatively, the flexible body of such a catheter can include a housing in its distal region for accommodating the x-ray generator unit 20. Further, the flexible body of such a catheter can include a channel extending from its proximal end to its distal end in which the flexible cable 28 can be disposed. Alternatively, the flexible cable can be disposed on the external wall of the flexible body of the catheter. Those skilled in the art will appreciate that structures for the flexible body other than those described above, and other modes of coupling the generator unit and the flexible cable to the flexible body of the catheter, can also be utilized. With reference to FIG. 3, the x-ray generating unit 20 includes a housing 44 in which the miniature transformer 26 and the miniature x-ray generator 24 are disposed. The exemplary housing 44 has a circular cross-section, although other cross-sectional shapes can also be utilized, with a diameter that is preferably less than about 4 millimeters, for example, in range of about 1 to about 3 millimeters, and a length that is in a range of about 20 to 50 millimeters. A portion 46 of the housing 44 is evacuated for accommodating various components of the x-ray generator 24. The housing 44 is preferably formed of a metal, such as, stainless steel, and can be electrically grounded via electrical and mechanical coupling to the outer conductor 40 of the flexible cable 28 (or a third ground wire). The exemplary x-ray generator 24 includes a cathode 48 separated from an anode 50 along an axial direction A of the housing 44. In this embodiment, the cathode 48 is a field emitter cathode, formed for example of tungsten, that emits electrons during a negative portion of each cycle of an AC voltage applied thereto by a secondary winding of the transformer 26, as described in more detail below. A support element 52, in the form of an annular ring that is mechanically coupled to the housing 44, can be used to position the cathode 48 centrally within the housing 44, and provide a vacuum-tight coupling with the cathode 48 to ensure that the portion 46 of the housing 44 is maintained at a sufficiently low pressure, e.g., a pressure in a range of about 10xe2x88x927 torr to about 10xe2x88x925 torr, to allow operation of the x-ray generator 24. The miniature x-ray generator 24 can further include a heat sink 54, for example, in the form of a solid cylinder formed of a metal, such as copper, that is coupled mechanically and electrically at one end to the housing 44, and at its other end to the anode 50. The heat sink 54 can be connected to the housing and/or the anode by utilizing any suitable technique. For example, the heat sink 54 can be soldered or braised to the housing and/or the anode. Alternatively, the heat sink and the housing can be machined as a monolithic structure. The heat sink 54 mechanically supports the anode 50 within the housing 44, and removes heat from the anode 50 during the operation of the x-ray generator 24. Further, the heat sink 54 maintains the anode 50 at the ground electrical potential via its coupling to the housing 44, which, as described above, can be maintained at the ground electrical potential. It is well known that metals with high atomic numbers, so-called high Z metals, are particularly suitable for efficient production of x-ray radiation. Accordingly, the anode 50 is preferably formed of a high-Z refractory metal, such as tungsten. With continuing reference to FIG. 3, the exemplary miniature x-ray generator 24 further includes an x-ray transmissive window 56 that allows transmission of the generated x-ray radiation to the outside environment. The window 56 has preferably a transmission coefficient of approximately 99% or higher for x-ray radiation having an energy in a range of about 10 keV to about 40 keV. With reference to FIG. 4A, in this exemplary embodiment, the window 56 can be formed of a plurality of beryllium window sections, such as sections 58a, 58b, herein collectively referred to as window sections 58, disposed in the metal housing 44, and spanning a circumference of a portion of the cylindrical housing to provide an approximately 360 degree field of view, or a smaller fraction thereof, depending on the application of the x-ray radiation, for transmission of the generated x-rays to the outside environment. Each beryllium window section 58 can be formed, for example, as a curved structure, such as that shown in FIG. 4B, having the same radius of curvature as that of the cylindrical housing and a thickness in a range of about 10 to about 100 microns. With reference to FIGS. 4C and 4D, in some embodiments, each beryllium window section 58 can be supported by a mesh 60, herein referred to as xe2x80x9cwafflexe2x80x9d support formed, for example, of a metal such as stainless steel. The mesh 60 can be mechanically coupled to the housing 44, and can include protrusions 60a in the form of metal xe2x80x9cribsxe2x80x9d for contact with the beryllium window section that it supports. Those having ordinary skill in the art will appreciate that materials, such as, diamond-like carbon or diamond, can also be employed to construct x-ray transmissive windows for use in a catheter of the invention. Referring again to FIG. 3, the x-ray generator 24 can optionally include an extraction electrode 62 coupled to the housing 44 via a support element 64 to be positioned in proximity of the cathode 48. The support element 64 can be, for example, an annular ring, formed of an insulating material, which is coupled to the inner surface of the housing 44. The support elements 52 and 64 can be formed as a monolithic unit, as shown in this embodiment, or alternatively as separate structures. The extraction electrode 62 is maintained at an electric potential that is intermediate that of the cathode 48 and the anode 50, as described in detail below, to control electron emission from the cathode 48, and to focus the electrons emitted from the cathode onto the anode. With continuing reference to FIG. 3, the exemplary miniature transformer 26 includes a core 66, which is preferably formed of a ferromagnetic material, such as iron or a ferrite composed of oxides of Fe, Ni, Mn and Zn. The exemplary core 66 is in the form of an elongate cylinder having a diameter in a range of about 0.1 millimeters to about 2 millimeters, and a length in a range of about 5 millimeters to about 30 millimeters. The core 66 can be electrically isolated or can be connected electrically to the inner conductor 36 of the coaxial cable 28, whose outer conductor 40 is electrically coupled to the metal housing 44 in order to maintain the housing at a ground electrical potential. The transformer 26 further includes a primary winding 68 in the form of a coil having a number of turns in a range of about 5 to about 60 turns that are wound on the ferrite core 66. The primary winding 68 is connected electrically at one end 68a to the inner (non-grounded) conductor of the input power cable, and at its other end 68b to the housing 44. Thus, a voltage differential between the inner and the outer conductors (36, 40) of the cable 28 is applied across the primary winding to induce a current therein, and consequently a magnetic flux within the core 66, as discussed in more detail below. The primary winding coil can be formed, for example, of copper wire having a diameter in a range of approximately 0.16 millimeters (#34 gauge wire) to approximately 0.57 millimeters (#23 gauge). Alternatively, a ribbon can be utilized to form the primary winding 68. A coil forming the primary winding is preferably wound tightly around the ferrite core 66 so as to produce negligible effect on the overall diameter of the transformer. The transformer 26 further includes a secondary winding 70 in the form of a coil having a number of turns in a range about 100 to about 1000 turns that are wound on the ferrite core 66. The coil 70 can be formed, for example, of copper wire having a diameter of approximately 0.080 millimeters and a resistance of about 3.85 ohm/meter, e.g., #40 gauge copper wire. The secondary winding 70 is coupled at one end 70a to the housing 44, and is coupled, mechanically and electrically, at its other end 70b, herein referred to as primary tap, to the cathode 48 to apply a voltage in a range of about 10 kV to about 40 kV thereto. The secondary winding 70 is connected electrically at a secondary tap 70c to the extraction electrode 62 in order to apply a voltage, which is less than the voltage applied to the cathode 48, thereto. The exemplary ferrite core 66, and the primary and secondary windings 68 and 70 can be xe2x80x9cpottedxe2x80x9d in an insulator 72, such as, silicone, epoxy, polyethylene, polyimide or Teflon(trademark), that electrically insulates these components from the housing 44. The insulator 72 is preferably selected so as to withstand an electrical potential difference of at least 40 kV. The primary and the secondary windings of the exemplary transformer 26 exhibit an inductance to resistance ratio (L/R) that is significantly higher than the inverse of the voltage frequency. For example, at a frequency (f) of 1 MHz, the inductance to resistance ratio of the secondary winding 70 having 600 turns (and a diameter of 2.1 mm including insulation for 40 kV potential difference, wound on a ferrite core having a magnetic permeability of 100) is approximately 3xc3x9710xe2x88x924 s, which is approximately three orders of magnitude greater than (2xcfx80f)xe2x88x921=1.6xc3x9710xe2x88x927 s. With reference to FIG. 5A, in operation, the primary winding 68 of the transformer 26 (FIG. 3) receives an input AC voltage from the power supply 34 (FIG. 1), via the inner conductor 36 of the electrical cable 28 (FIG. 3). The power supply 34 can have a transformer 74 that receives the AC voltage at a primary winding 74a, and generates an output voltage having an rms amplitude in a range of about 100 V to about 4 kV at a secondary winding 74b. This output voltage is applied, via the inner conductor 36 of the cable 38, to the primary winding 68 of the miniature transformer 26, and generates an AC current in a range of about 200 microamperes to about 5 milliamperes therein. The AC current through the primary winding 68 in turn generates a time-varying magnetic flux in the core 66 (FIG. 3), and consequently in the secondary winding 70. This time-varying magnetic flux induces a voltage across the secondary winding 70. Because the number of turns of the coil forming the secondary winding is approximately 40 to 100 times higher than that of the primary winding, the voltage induced in the secondary winding has an rms value in a range of about 10 to 40 kV, and more preferably, in a range of about 20 to about 30 kV (rms). The induced voltage at the primary tap 70a, which equals the voltage generated across the entire secondary winding 70, is applied to the cathode 48, thereby generating a time-varying electric field between the cathode 48 and the anode 50, which is maintained at a ground electric potential. The AC voltage applied to the cathode further causes emission of electrons therefrom during each negative swing of the voltage. Further, the voltage induced at the secondary tap 70c, which equals a selected fraction of the voltage induced across the entire secondary winding, is applied to the extraction electrode 62. The electric field established between the cathode 48 and the anode 50 accelerates these electrons to energies in a range of about 10 keV to about 40 keV upon impact with the anode. The impact of the electrons with the anode causes generation of x-ray radiation. As discussed above, the anode is preferably formed of a high-Z metal to enhance the x-ray production. Electrons with an energy of about 30 keV typically convert between about 0.05% to 0.25% of their kinetic energy into x-ray energy when they impinge on a high-Z metal, such as tungsten. A portion of the x-ray radiation that escapes to the outside environment through the window 56 can be utilized for a variety of different applications, as discussed in more detail below. With reference to FIG. 5B, in another embodiment, the exemplary transformer 26 also includes another secondary winding 76 that is formed of a coil having approximately 20 to 200 turns, and is wound on the ferrite core 66 shown in FIG. 3. This secondary winding 76 is mechanically and electrically coupled at one end to the extraction electrode 62 to apply a voltage thereto, which is intermediate the voltage difference between the cathode and the anode. Further, the time-varying magnetic flux generated by the current in the primary winding 68 induces a voltage in the second secondary winding 76, which is applied to the extraction electrode 62. Because the number of turns of the coil forming the winding 76 is less than that of the winding 70, e.g., 120 turns compared to 600 turns, the voltage induced across the winding 76 is less than that induced in the winding 70, e.g., in range of about 2 to 8 kV. The application of this intermediary voltage to the extraction electrode helps guide the electrons emitted from the cathode 48 to the anode 50. An x-ray generator unit in accordance with the teachings of the invention, such as the exemplary unit 20 described above, provides a number of distinct advantages. For example, it is sufficiently small to be coupled to the tip of a catheter having an outer diameter of a few millimeters, thereby permitting its use, for example, within a patient""s artery. Further, the close proximity of the step-up transformer to the x-ray generator obviates the need for transmission of high voltages, e.g., in the range of 10 to 40 kV, from an external power supply, along an electrical cable that extends from the proximal end to the distal end of the catheter, to the x-ray generator. Rather, the electrical cable in a catheter of the invention carries much lower voltages, e.g., in a range of about 100 V to about 4 kV. This allows the use of a more flexible cable in a catheter of the invention, and further enhances operational safety of the catheter. The term xe2x80x9cproximityxe2x80x9d as used herein to describe the spatial relationship of the transformer and x-ray generator is extended to describe separation distances less than about 50 millimeters, typically on the order of a few millimeters or less. Thus, in a catheter of the invention, high electrical voltages are confined to the step-up transformer and its associated x-ray generator. This advantageously enhances the operational safety of the catheter, especially in medical applications in which the catheter is inserted in a patient""s lumen. Further, the lowering of the voltage transmitted by the flexible cable allows utilizing a thinner insulation layer for the cable, thereby resulting in a more flexible cable that enhances the overall flexibility of the catheter. In addition, in a catheter of the invention, the transformer can be advantageously powered by a low-cost AC frequency converter. Hence, a catheter of the invention not only exhibits enhanced safety and flexibility but it can also be constructed in a cost efficient manner. In fact, a catheter of the invention can be constructed as a single-use item. A catheter of the invention can be utilized in a number of different applications. In one such application, it is employed in medical procedures to deliver highly localized, biologically effective doses of ionizing radiation to a patient""s tissue. For example, a catheter of the invention can be utilized to deliver an x-ray dose in a range of about 8 Gray to about 20 Gray (800 to 2000 rads) to a localized portion of a patient""s tissue. The x-ray radiation can be effective, for example, in preventing restenosis. In addition, the x-ray radiation can be employed for interstitial radiosurgery of tumors. It is clear to those skilled in the art that the catheter of the invention can find numerous other medical applications. Although in the embodiments described above, the x-ray generator 24 includes one cathode and one anode, in other embodiments of the invention, the x-ray generator can include a plurality of cathodes and anodes to more efficiently utilize an AC voltage for generating x-ray radiation. For example, FIG. 6 depicts an x-ray generator 78 according to the invention that includes two cathodes 80 and 82, which can be field emission cathodes formed of tungsten, and two anodes 84 and 86 each of which is in the form of an annular ring formed, for example, of tungsten. The cathode 80 and the anode 84 are coupled to the secondary winding 70 of the transformer 26 such that the positive and negative swings of the voltage across the secondary winding 70 are applied to the cathode 80 and the anode 84. In contrast, the cathode 82 and the anode 86 are grounded. During a negative swing of the voltage across the secondary winding 70, the cathode 80 emits electrons that are accelerated to the anode 86 to impact that anode, thereby generating x-ray radiation. Further, during a positive swing of the voltage induced across the secondary winding 70, the cathode 82 emits electrons which are accelerated towards the anode 84, which during a positive voltage swing is at a higher electrical potential, and cause generation of x-ray radiation upon impact with that anode. Hence, in this manner, x-ray radiation is generated during the entire period of each cycle of an AC voltage induced in the secondary winding of the transformer 26, rather than during only one-half of each cycle. Miniature x-ray generators, having multiple cathodes and anodes, which can be utilized in a catheter of the invention as x-ray sources are not limited to the x-ray generator 78, described above. For example, FIG. 7 depicts another x-ray generator 88 according to the teachings of the invention which also includes two cathodes 90 and 92 and two anodes 94 and 96. In contrast to the x-ray generator 78, the cathode 90 and the anode 94, and similary, the cathode 92 and the anode 96, are not held at the same electrical potential. Rather, while the cathode 90 is connected across the entire secondary winding at a primary tap 70b, the anode 94 is connected across a portion of the secondary winding at a secondary tap 70c. Further, while the cathode 92 is grounded, the anode 96 is connected across a portion of the secondary winding of the transformer at a tertiary tap 70d. This arrangement allows the anodes 94 and 96 to function not only as anodes but also as extraction electrodes in alternative positive and negative voltage swings of the voltage induced across the secondary winding 70. The embodiments of the invention described above are intended to be interpreted as illustrative and not in a limiting sense. Those skilled in the art shall be able to make numerous variations and modifications to the above embodiments without departing from the scope of the invention. For example, materials other than those described above can be utilized to form the cathode and the anode of the x-ray generator. In addition, those skilled in the art can readily utilize the teachings of the invention for constructing a miniature x-ray generator that includes more than two cathodes and two anodes.