WO2014155283A1 - Radiation application device - Google Patents

Radiation application device Download PDF

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Publication number
WO2014155283A1
WO2014155283A1 PCT/IB2014/060121 IB2014060121W WO2014155283A1 WO 2014155283 A1 WO2014155283 A1 WO 2014155283A1 IB 2014060121 W IB2014060121 W IB 2014060121W WO 2014155283 A1 WO2014155283 A1 WO 2014155283A1
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WO
WIPO (PCT)
Prior art keywords
radiation application
radiation
application device
oxygen
tissue region
Prior art date
Application number
PCT/IB2014/060121
Other languages
French (fr)
Inventor
Carolina Ribbing
Gereon Vogtmeier
Original Assignee
Koninklijke Philips N.V.
Philips Deutschland Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Koninklijke Philips N.V., Philips Deutschland Gmbh filed Critical Koninklijke Philips N.V.
Publication of WO2014155283A1 publication Critical patent/WO2014155283A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1001—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1001—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
    • A61N5/1027—Interstitial radiation therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N2005/002—Cooling systems
    • A61N2005/005—Cooling systems for cooling the radiator
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1001—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
    • A61N5/1002—Intraluminal radiation therapy
    • A61N2005/1003—Intraluminal radiation therapy having means for centering a radioactive source within the lumen, e.g. balloons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1001—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
    • A61N2005/1019—Sources therefor
    • A61N2005/1022—Generators, e.g. X-ray tubes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1048—Monitoring, verifying, controlling systems and methods
    • A61N5/1049—Monitoring, verifying, controlling systems and methods for verifying the position of the patient with respect to the radiation beam
    • A61N2005/1055—Monitoring, verifying, controlling systems and methods for verifying the position of the patient with respect to the radiation beam using magnetic resonance imaging [MRI]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1048—Monitoring, verifying, controlling systems and methods
    • A61N5/1049—Monitoring, verifying, controlling systems and methods for verifying the position of the patient with respect to the radiation beam
    • A61N2005/1058—Monitoring, verifying, controlling systems and methods for verifying the position of the patient with respect to the radiation beam using ultrasound imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1048—Monitoring, verifying, controlling systems and methods
    • A61N5/1049—Monitoring, verifying, controlling systems and methods for verifying the position of the patient with respect to the radiation beam
    • A61N2005/1061—Monitoring, verifying, controlling systems and methods for verifying the position of the patient with respect to the radiation beam using an x-ray imaging system having a separate imaging source
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N2005/1085—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy characterised by the type of particles applied to the patient
    • A61N2005/1091—Kilovoltage or orthovoltage range photons

Definitions

  • the invention relates to a radiation application device, a radiation application method and a radiation application computer program for applying radiation to an inner tissue region of a living being.
  • the invention further relates to apparatuses and systems comprising the radiation application device.
  • EVIOG implantable micro-oxygen generator
  • An oxygen generator is therefore implanted in the tumor cells, wherein the oxygen generator is ultrasonically powered and is adapted to perform in situ electrolysis for generating the oxygen.
  • the high-energy photons generated with the linear accelerator traverse healthy tissue before reaching the tumor cells, thereby also affecting the healthy tissue.
  • the directing of the high-energy photons to a desired location within the person is not very accurate such that it is difficult to direct the high-energy photons accurately to the location at which the oxygen is generated. This reduces the quality of the radiation treatment.
  • a radiation application device for applying radiation to an inner tissue region of a living being, wherein the radiation application device is adapted to be inserted into the inner tissue region and comprises:
  • an integrated x-ray source for applying x-rays to the inner tissue region
  • an integrated oxygen providing unit for providing oxygen to the inner tissue region
  • the x-ray source can directly be inserted into the living being, which is preferentially a person or an animal, at a location at which the inner tissue region is present.
  • the x-ray source can be inserted directly into or directly adjacent to a tumor region within the living being.
  • the x-rays can therefore very accurately be applied to the inner tissue region.
  • the x-ray source and the oxygen providing unit are integrated in a single radiation application device, the x-rays can very easily and accurately be applied to exactly the inner tissue region, where the oxygen providing unit provides the oxygen, if the radiation application device has been inserted into the inner tissue region. This improves the quality of treating the inner tissue region.
  • the radiation application device is preferentially an interventional radiation application device, which combines the functionality of radiation generation by the x-ray source and the local in situ application of oxygen to the inner tissue region, which may be a tumor region, for performing an internal radiotherapy, i.e. an internal brachytherapy, wherein the oxygen can be supplied to the inner tissue region such that the oxygenated tissue is in the same area as the area irradiated by the x-rays.
  • an interventional radiation application device which combines the functionality of radiation generation by the x-ray source and the local in situ application of oxygen to the inner tissue region, which may be a tumor region, for performing an internal radiotherapy, i.e. an internal brachytherapy, wherein the oxygen can be supplied to the inner tissue region such that the oxygenated tissue is in the same area as the area irradiated by the x-rays.
  • the x-ray source which is preferentially a miniature x-ray source, is preferentially adapted to be used for the treatment of solid tumors in situ. It preferentially comprises a cathode, an anode and an intermediate dielectric.
  • the cathode may be, for example, a thermal filament, a field emitting cathode, a Schottky cathode, a piezo- or ferroelectric cathode, or a combination thereof.
  • a further electrode, a gate can be incorporated, for instance, in form of a floating or cathode potential electrostatic lens.
  • the anode can be a reflection or transmission type anode.
  • the x-ray source is preferentially operated with a voltage within the range of 20 to 100 kV, in order to produce spectra in the millimeter to centimeter range in tissue.
  • the operating current is preferentially chosen so as to produce a dose rate being high enough for treating the inner tissue region.
  • the operating current which can also be regarded as being a tube current, is therefore preferentially within the range of 20 to 800 ⁇ .
  • the source can be powered in vivo through, for instance, a miniature high voltage cable, ultrasound et cetera.
  • the oxygen providing unit is adapted to produce the oxygen by electrolysis of water.
  • the oxygen providing unit is preferentially adapted to produce the oxygen in situ at the location where the x-rays are applied to the inner tissue region. This allows providing the oxygen directly at the location, at which it is really needed, in a relatively simple way, without necessarily requiring, for instance, an external oxygen storage means like a gas cylinder and a tube for guiding the oxygen from the outside of the living being to the inner tissue region.
  • the oxygen providing unit preferentially comprises an electrolysis electrode for producing the oxygen by the electrolysis of water, wherein the radiation application device is adapted such that in use the electrolysis electrode is contactable with tissue within the living being.
  • the oxygen providing unit which is preferentially adapted to produce the oxygen by electrolysis of water, is preferentially integrated with the x-ray source.
  • the x-ray source may comprise the electrolysis electrode for producing the oxygen by electrolysis of water, wherein the x-ray source is adapted such that in use the electrolysis electrode is contactable with tissue within the living being.
  • the electrolysis electrode may be formed at least partly by the anode, i.e. the x-ray source may be adapted to use the operating current for producing the oxygen in vivo, wherein the x-ray source can be adapted to use the whole operating current or only a part of the operating current for the electrolysis. This allows for a very compact configuration of the x-ray source and the oxygen providing unit, which can lead to a very small combined x-ray source/oxygen providing unit.
  • the x-ray source comprises a first electrode being a cathode and a second electrode being an anode, wherein the electrolysis electrode is a third electrode.
  • the radiation application device may comprise, besides the cathode and the anode of the x-ray source, a third electrode, which may be arranged on the surface of the radiation application device or which may form at least a part of the surface of the radiation application device, for performing the electrolysis. Since this further electrode is not used for generating the x-rays, i.e. since the further electrode does not need to be optimized for the generation of x-rays, it can be shaped more freely.
  • the electrolysis electrode may be electrically connected to the anode.
  • the radiation application device may also be adapted such that a) the voltage at the cathode and/or the anode and b) the voltage at the electrolysis electrode are independently from each other suppliable.
  • the voltage supply for the x- ray source may be independent of the voltage for the electrolysis electrode.
  • the radiation application device may comprise an electrical conductor for electrically connecting the electrolysis electrode to a voltage supply outside the living being, wherein this electrical conductor may not electrically connect the anode and/or the cathode to a voltage supply outside of the living being.
  • the radiation application device may therefore comprise an extra electrical conductor, in particular, an extra cable, from the outside for supplying voltage to the electrolysis electrode. This allows optimizing the voltage supply to a) the cathode and/or the anode and b) to the electrolysis electrode independently from each other, which can lead to an improved x-ray application and an improved oxygen generation, which in turn can further improve the radiation treatment.
  • the electrolysis electrode is electrically connected to the cathode via a voltage reduction unit for using a reduced voltage for the electrolysis.
  • the voltage for the electrolysis electrode may be supplied from the internal cathode potential of the x-ray source.
  • the voltage reduction unit may be a voltage divider using a resistor network or another means for reducing the voltage to a life safe low voltage. The same voltage supply may therefore be used for providing the voltage to the cathode and for providing the voltage to the electrolysis electrode, without necessarily requiring two voltage supplies. This can improve the handling of the radiation application device.
  • the radiation application device comprises an insertion element having a distal tip, wherein the x-ray source and the oxygen providing unit are arranged at the distal tip of the insertion element.
  • the oxygen providing unit may comprise an electrolysis electrode for producing the oxygen by electrolysis, wherein the x-ray source and the oxygen providing unit are arranged at the distal tip of the insertion element such that in use the electrolysis electrode is contactable with tissue within the living being.
  • the x-ray source may form the distal point of an insertion element like a needle, for example, a biopsy-like needle, in order to insert the x-ray source, which may comprise an integrated oxygen providing unit, in vivo.
  • the insertion element is inflatable at the distal tip, wherein the oxygen providing unit comprises an electrolysis electrode arranged on an outside surface of the inflatable distal tip, which may lead to a further improved contact between the electrolysis electrode and the tissue.
  • the radiation application device may comprise a cooling element for cooling the electrolysis electrode.
  • the radiation application device comprises an insertion element having a distal tip, wherein the x-ray source and the oxygen providing unit are arranged at the distal tip of the insertion element such that in use the electrolysis electrode of the x-ray tube is contactable with tissue within the living being, the cooling element may be integrated in the insertion element.
  • the cooling element is therefore preferentially small enough to fit into the insertion element, especially to fit into a needle.
  • the oxygen providing unit comprises a delivery tube for delivering the oxygen from an outside location, which is outside the living being, to the inner tissue region.
  • the oxygen may be delivered to the location, where the x-ray source is located within the living being, by using a tube.
  • the delivery tube may be integrated with an insertion element for inserting the x-ray source into the living being.
  • the insertion element may be regarded as being a source applicator for inserting the x-ray source at a desired position within the living being.
  • the delivery tube may therefore be integrated with the source applicator.
  • the x-ray source and the oxygen providing unit which in this embodiment comprises a delivery tube with a distal opening, can be placed relatively easily within or adjacent to the inner tissue region by placing the tip of the insertion element accordingly.
  • a radiation application apparatus for applying radiation to an inner tissue region of a living being, wherein the radiation application apparatus comprises:
  • a power supply connected to the x-ray source of the radiation application device for powering the x-ray source.
  • a radiation application system for applying radiation to an inner tissue region of a living being comprising:
  • an imaging apparatus for imaging the radiation application device within the living being.
  • a radiation application method for applying radiation to an inner tissue region of a living being by using a radiation application device as defined in claim 1, which has been inserted into the living being is presented, wherein the radiation application method comprises applying x-rays of the x-ray source of the radiation application device to the inner tissue region and providing oxygen by using the oxygen providing unit of the radiation application device to the same inner tissue region.
  • the application of the x-rays and the provision of the oxygen to the same inner tissue region are preferentially performed concurrently.
  • a radiation application computer program for applying radiation to an inner tissue region within a living being by using a radiation application apparatus as defined in claim 12 is presented, wherein the radiation application computer program comprises program code means for causing the radiation application apparatus to carry out the steps of the radiation application method as defined in claim 14, when the radiation application computer program is run on a computer controlling the radiation application apparatus.
  • the radiation application device of claim 1 the radiation application apparatus of claim 12, the radiation application system of claim 13, the radiation application method of claim 14, and the radiation application computer program of claim 15 have similar and/or identical preferred embodiments, in particular, as defined in the dependent claims.
  • Fig. 1 shows schematically and exemplarily an embodiment of a radiation application system for applying radiation to an inner tissue region of a living being
  • Fig. 2 shows schematically and exemplarily an embodiment of a radiation application device comprising an integrated x-ray source and an integrated oxygen providing unit
  • Fig. 3 shows a flowchart exemplarily illustrating a radiation application method for applying radiation to an inner tissue region of a living being
  • Figs. 4 to 6 and 8 show schematically and exemplarily further embodiments of a radiation application device comprising an integrated x-ray source and an integrated oxygen providing unit, and
  • Fig. 7 schematically and exemplarily illustrates a voltage reduction unit between a cathode and an electrolysis electrode.
  • Fig. 1 shows schematically and exemplarily an embodiment of a radiation application system for applying radiation to an inner tissue region of a living being.
  • the radiation application system is a brachytherapy system 1 for applying x-rays to an inner tumor region 7 within a person 6 lying on a support means like a patient table 8.
  • the brachytherapy system 1 comprises a radiation application apparatus 3 with a radiation application device 4 and a power supply 15 for powering the radiation application device 4.
  • the radiation application device 4 comprises an insertion element 5 having a distal tip 21, wherein a miniature x-ray source for applying x-rays to the inner tumor region 7 is arranged at the distal tip 21 of the insertion element 5.
  • the x-ray source has an integrated oxygen providing unit such that at the distal tip 21 also oxygen can be provided to the inner tissue region 7.
  • the insertion element 5 is a biopsy needle for placing the x-ray source and the oxygen providing unit in vivo within or adjacent to the tumor region 7.
  • the insertion process can be monitored by using an imaging apparatus 2 for imaging the radiation application device 4 within the person 6.
  • the imaging apparatus 2 comprises an imaging radiation source 9 for generating imaging radiation 10 for traversing the person 6 with the inner tumor region 7.
  • the imaging radiation source 9 is an imaging x-ray tube and the imaging radiation 10 are imaging x-rays.
  • the imaging radiation 10 is detected by an imaging radiation detector 11 being, in this embodiment, an imaging x-ray detector.
  • the imaging radiation detector 11 provides detection values, which are indicative of the detected imaging radiation, to an imaging control unit 12, which generates projection images based on the received detection values.
  • the projection images are shown to a user like a physician by using a display 13.
  • the imaging radiation source 9 and the imaging radiation detector 11 can be mounted on a C-arm, in order to allow the imaging apparatus 2 to acquire projection images in different projection directions.
  • the imaging apparatus 2 which can also be regarded as being a fluoroscopy apparatus
  • another imaging apparatus may be used for monitoring the insertion of the insertion element 5 into the inner tumor region 7 within the person 6 like an ultrasound imaging apparatus, an x-ray computed tomography imaging apparatus, a magnetic resonance imaging apparatus, et cetera.
  • the x-ray source with the integrated oxygen providing unit is schematically and exemplarily illustrated in Fig. 2.
  • the x-ray source 19, which is preferentially adapted to be used for the treatment of solid tumors in situ and preferentially not for the irradiation of tumor cavities like in accelerated partial breast irradiation procedures, comprises a cathode 18, an anode 20 and an intermediate dielectric (not shown in Fig. 2).
  • the cathode 18 is a thermal filament.
  • the cathode 18 can also be a field emitting cathode, a Schottky cathode, a piezo-or ferroelectric cathode, or a combination thereof.
  • the anode 20 can be a reflection or transmission type anode.
  • the x-ray source 19 is operated with a voltage within the range of 20 to 100 kV by the voltage supply 15, in order to produce spectra in the millimeter to centimeter range in the tissue.
  • the operating current is preferentially chosen so as to produce a dose rate being high enough to treat the inner tissue region 7, i.e. it is preferentially within the range of 20 to 800 ⁇ .
  • the x-ray source 19 is powered in vivo by the voltage supply 15 via a miniature high voltage cable, wherein at the cathode 18 a negative high voltage is applied and the anode 20 and the person 6 are connected to ground.
  • the anode 20 fulfills two functions, i.e. it is the anode of the x-rays generation process and it is an electrolysis electrode for producing the oxygen by electrolysis of water. In this way the oxygen can be produced in situ at the location where the x-rays are applied to the inner tissue region 7.
  • the x-ray source 19 is configured such that the electrolysis electrode 20, i.e. the anode 20, is in contact with the inner tissue region 7 within the person 6, if the tip 21 of the needle 5 has been inserted into the inner tissue region 7. It should be noted that Fig.
  • step 101 the system is initialized and prepared for applying the radiation and providing the oxygen to the tumor tissue region 7.
  • the distal tip 21 of the needle 5 is inserted into the inner tumor region 7 under guidance of projection images generated by the imaging apparatus 2.
  • step 102 x-rays are generated by the x-ray source 19 and applied to the inner tumor region 7, while concurrently oxygen is provided by the oxygen providing unit in step 103.
  • the radiation application method ends in step 104.
  • the provision of oxygen may be performed immediately before applying the radiation.
  • steps 102 and 103 may be performed in a loop, wherein within the loop step 102 is performed before step 103.
  • the radiation application device may comprise a first electrode being the cathode of the x-ray source, a second electrode being the anode of the x-ray source and a third electrode being the electrolysis electrode, wherein the electrolysis electrode can be electrically connected to the anode.
  • the radiation application device may comprise, besides the cathode and the anode of the x-ray source, a further electrode on the surface of the radiation application device or forming at least a part of the surface of the radiation application, in particular, on the surface of the tip of the insertion element or forming at least a part of the surface of the tip of the insertion element, for performing the electrolysis as schematically and exemplarily illustrated in Fig. 4.
  • the radiation application device 204 comprises an insertion element 205 having at its distal tip 221 an x-ray source 219 with a cathode 218 and an anode 220, and a third electrode 230 being an electrolysis electrode, wherein the electrolysis electrode 230 is arranged at the outside of the tip 221 such that the electrolysis electrode 230 is contactable with tissue within the person 6.
  • the electrolysis electrode 230 is electrically connected with the anode 220 via an electrical connection 231 like an electrical wire, and the cathode 218 is electrically connected with the power supply 15 via an electrical
  • connection 250 like a cable.
  • the electrolysis electrode is arranged at the outside of the tip of the insertion element
  • the electrolysis electrode can also be arranged at another location at the outside of the insertion element.
  • the radiation application device 304 can comprise an insertion element 305 with an x-ray source, which has a cathode 318 and an anode 320 and which is embedded in insulating material 332, and with a third electrode 330 being an electrolysis electrode circumferentially arranged at an outside side wall of the insertion element 305 close to the tip 321 of the insertion element 305.
  • the electrolysis electrode 330 is electrically connected with the anode 320 via an electrical connection 331 like an electrical wire.
  • the cathode 318 can be connected with the power supply 15 via an electrical connection 350 being, for instance, a cable.
  • a radiation application device 404 is adapted such that the voltage at the cathode 418 and the voltage at the electrolysis electrode 430 are suppliable independently from each other.
  • the radiation application device 404 comprises an electrical conductor 436 for electrically connecting the electrolysis electrode 430 to a voltage supply outside the person, wherein the electrical conductor 430 does not electrically connect the cathode 418 or the anode 420 to a voltage supply outside the person 6.
  • the electrical conductor 430 is an extra cable from the outside for supplying voltage to the electrolysis electrode.
  • the insertion element 405 is a balloon insertion element with an inflatable part 434, which is shown in Fig.
  • the outside of the inflatable part 434 comprises the electrolysis electrode 430.
  • the inflatable part 434 can be inflated by using an external pump and an internal tube 433 within the insertion element 405.
  • the cathode 418 and the anode 420 are electrically connected with the power supply 15 outside of the person 6 via electrical connections 450, 435 being preferentially electrical cables.
  • an integrated x-ray source 419 for applying x-rays to the inner tissue region 7 of the person 6 and an integrated electrolysis electrode 430 forming an integrated oxygen providing unit for providing oxygen to the same inner tissue region 7 are provided.
  • the electrolysis electrode can be separately supplied by voltage using an extra electrical conductor.
  • the electrolysis electrode can also be electrically connected to the cathode via a voltage reduction unit for using a reduced voltage for the electrolysis of the water.
  • a corresponding electrical configuration is schematically and exemplarily illustrated in Fig. 7.
  • Fig. 7 an x-ray source 519 and an electrolysis electrode 530 of a radiation application device are shown.
  • the x-ray source 519 comprises a cathode 518 and an anode 520, wherein the electrolysis electrode 530 is electrically connected to the cathode 518 via a voltage reduction unit 540 and wherein the cathode 518 is electrically connected to the power supply 15.
  • the voltage reduction unit 540 is a voltage divider comprising resistors 542, 543.
  • Fig. 7 just illustrates the electrical configuration of an embodiment with an electrolysis electrode receiving voltage from the cathode of the x-ray source via a voltage reduction unit, i.e. also in this case an insertion element and further elements of the radiation application device, which are not shown in Fig. 7 for clarity reasons, are preferentially present.
  • a voltage reduction unit i.e. also in this case an insertion element and further elements of the radiation application device, which are not shown in Fig. 7 for clarity reasons, are preferentially present.
  • the electrical configuration illustrated in Fig. 7 can be used with the embodiments shown in Figs. 4 and 5, if in these embodiments the electrolysis electrode is not electrically connected to the anode, but via a voltage reduction unit with the cathode.
  • the radiation application device 604 includes a delivery tube 651 for delivering the oxygen from an outside location, which is outside the person, to the inner tissue region.
  • a delivery tube 651 for delivering the oxygen from an outside location, which is outside the person, to the inner tissue region.
  • an oxygen storage unit like an oxygen gas cylinder and an oxygen control unit may be provided, in order to allow the flow of the oxygen from the outside of the person 6 to the inner tissue region through the delivery tube 651 in a controlled way.
  • the oxygen providing unit may then be formed by the delivery tube 651, especially by the distal opening of the delivery tube.
  • the delivery tube 651 is integrated with an insertion element 605 like a needle for inserting the x-ray source 619 into the person 6.
  • the insertion element 605 may be regarded as being a source applicator for inserting the x-ray source 619 at a desired position within the person 6.
  • the x-ray source 619 comprises a cathode 618 with an anode 620, wherein the cathode 618 and the anode 620 are electrically connected with the power supply 15 via electrical connections 650, 635.
  • the electrolysis electrode can be powered such that the electrolysis electrode is not heated to a temperature, which could harm the tissue.
  • parts of the tip of the insertion element, in particular, the anode of the x-ray tube may be cooled by using a cooling element.
  • a cooling element For instance, if in an embodiment oxygen is provided from the outside of the person to the distal tip of the insertion element via a delivery tube, the oxygen may be cooled, in order to cool the distal tip of the insertion element, in particular, the anode of the x-ray source.
  • the oxygen provision and the cooling can be integrated.
  • the cooling effect can also be provided by a separate cooling element like a cooling tube guiding cooling fluid to the distal tip and a further cooling tube for guiding the cooling fluid away from the distal tip, in order to provide a closed cooling loop, particularly if the oxygen is locally produced at the tip of the insertion element by using an electrolysis electrode.
  • the cooling element may also be formed by one or several cooling tubes for guiding the cooling fluid to the distal tip of the insertion element, wherein the distal tip can comprise one or several openings for allowing the cooling fluid to leave the distal tip.
  • the cooling fluid is biocompatible.
  • the cooling fluid may be water.
  • Tumor hypoxia is a condition involving tumor cell oxygen deprivation.
  • the blood supply through new capillaries is often lagging, especially in the center of the tumor.
  • Hypoxia reduces the sensitivity of tumor cells to both chemo- and radiotherapy.
  • radiotherapy the explanation of this phenomenon involves radiation produced oxygen free radicals as mediator of DNA damage. Oxygenation of tumors as a method of enhancing the treatment efficacy has been investigated for many years.
  • Systemic methods involve that the patient breathes gas mixtures with increased oxygen concentration. Such treatments are hampered by safety issues due to the high flammability of oxygen and by systemic side-effects like high fewer and asthma. Also, systemic methods lack special control of the oxygenation. As a remedy, an implantable micro-oxygen generator has been suggested for external beam radiotherapy in the above mentioned article. However, this combination of the implantable micro-oxygen generator with the external beam radiotherapy has several drawbacks and complications like the above mentioned difficulty to provide the application of the radiation and the provision of the oxygen accurately at the same location within a living being.
  • the radiation application device provides therefore an integration of electrolytical oxygen generation with a miniature tube to be used for electronic brachytherapy. This can make it possible to avoid an extra system for oxygenation and to avoid positioning problems.
  • the two systems i.e. radiotherapeutic and oxygen-providing, integrated, they are positioned together and in only one step, for example, by using a stiff biopsy-like needle containing the mini tube.
  • a simultaneous generation of oxygen locally in the tumor as an integrated part of a miniature x-ray tube inserted into a tumor may be provided.
  • the miniature x-ray tube may be operated at a modest voltage of, for instance, 50 kV.
  • the advantages include that the tube can be turned off and that the radiation energy is relatively low and thus has a short range. This implies that the treatment does not have to be carried out in, for example, a radiotherapy bunker, but can be given in interventional x-ray facilities and operation rooms. Therefore, radiotherapy is possible in various departments and outpatient settings and the treatment can be given by, for instance, an interventional radiologist. The healthy tissue of the patient and treatment personnel are spared.
  • the applied voltage gives the energy of the radiation, i.e. the maximum energy of the bremsstrahlung spectrum, and thus the radiation range in tissue.
  • An acceleration voltage of 50 kV gives a mean energy of about 25 keV.
  • the distance to the target tissue is about 0.5 to 4 cm, requiring radiation energy of about 20 to 50 keV. This means that the acceleration voltage of the miniature tube is preferentially between 50 to 100 kV.
  • the tube current i.e. the operating current, is preferentially in the range of 50 to 500 ⁇ .
  • the radiation application device comprises a miniature x-ray source for image guided interventional radiotherapy.
  • the miniature source may have an integrated electrolytical production of oxygen for oxygenation of hypoxic tumors simultaneously with the radiation therapy. Part of or the whole tube current can be used for electrolysis of water in vivo.
  • Very small miniature sources may be permanently implanted, similar to the standard low dose rate (LDR) isotopic brachytherapy. This means one or several x-ray sources with integrated oxygen production capability may be
  • a tumor intraoperatively or percutaneously placed into a tumor using, for instance, a syringe and using a wireless power transmission like a wireless ultrasound powering as disclosed, for example, in the above mentioned article.
  • the electrolysis reaction for generating the oxygen at the electrolysis electrode may be described by following equation: 40H “ (aq) ⁇ 0 2 (g) + 2H 2 0(l)+ 4e "
  • a corresponding reaction i.e. a reduction, produces H 2 , which is inert and which may be eliminated via the lungs.
  • a corresponding reaction i.e. a reduction
  • an electronic brachytherapy system comprising a miniature x-ray tube with in situ oxygen generation through water electrolysis.
  • the applications include, but are not limited to, a subgroup of isotopic and electronic brachytherapy applications, for instance, for treatment of prostate, pancreas, liver, rectum, and kidney cancer.
  • the embodiments may be adapted to be used for a percutaneous brachytherapy where a solid tumor is punctured by a needle containing a miniature x-ray source.
  • a percutaneous brachytherapy where a solid tumor is punctured by a needle containing a miniature x-ray source.
  • the described radiation application device is advantageous.
  • the radiation application device can also be adapted for other applications. For instance, since high oxygen levels increase
  • the radiation therapy device can also be adapted to be used for, for example, normoxic tumors or tumor regions.
  • a single unit or device may fulfill the functions of several items recited in the claims.
  • the mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage.
  • control of the radiation application apparatus in accordance with the above described radiation application method can be implemented as program code means of a computer program and/or as dedicated hardware.
  • a computer program may be
  • a suitable medium such as an optical storage medium or a solid-state medium, supplied together with or as part of other hardware, but may also be distributed in other forms, such as via the Internet or other wired or wireless telecommunication systems.
  • the invention relates to a radiation application device for applying radiation to an inner tissue region of a living being, particularly for treating tumors in situ.
  • the radiation application device is adapted to be inserted into the inner tissue region and comprises an integrated x-ray source for applying x-rays to the inner tissue region and an integrated oxygen providing unit for providing oxygen to the inner tissue region. Since both, the x-ray source and the oxygen providing unit, are integrated in a single radiation application device, the x-rays can very easily and accurately be applied to exactly the inner tissue region, where the oxygen providing unit provides the oxygen, if the radiation application device has been inserted into the inner tissue region. This improves the quality of treating the inner tissue region.

Abstract

The invention relates to a radiation application device for applying radiation to an inner tissue region of a living being, particularly for treating tumors in situ. The radiation application device (204) is adapted to be inserted into the inner tissue region and comprises an integrated x-ray source (219) for applying x-rays to the inner tissue region and an integrated oxygen providing unit (230) for providing oxygen to the inner tissue region. Since both, the x-ray source and the oxygen providing unit, are integrated in a single radiation application device, the x-rays can very easily and accurately be applied to exactly the inner tissue region, where the oxygen providing unit provides the oxygen, if the radiation application device has been inserted into the inner tissue region. This improves the quality of treating the inner tissue region.

Description

Radiation application device
FIELD OF THE INVENTION
The invention relates to a radiation application device, a radiation application method and a radiation application computer program for applying radiation to an inner tissue region of a living being. The invention further relates to apparatuses and systems comprising the radiation application device.
BACKGROUND OF THE INVENTION
The article "An ultrasonically powered implantable micro-oxygen generator (EVIOG)" by T. Maleki et al., IEEE Transactions on Biomedical Engineering, volume 58, number 11, pages 3104 to 3111 (2011) discloses a radiation therapy for destroying tumor cells using high-energy photons generated by a linear accelerator. Tumor cell death mainly results from direct and indirect DNA damage through ionizing radiation induced radiolysis of water. The efficacy of the radiation therapy generally depends inter alia on the concentration of oxygen in the tumor cells, because the presence of oxygen enables the creation of free radical species with larger stability and longer lifetimes that are critical for a permanent damage to the DNA. An oxygen generator is therefore implanted in the tumor cells, wherein the oxygen generator is ultrasonically powered and is adapted to perform in situ electrolysis for generating the oxygen. The high-energy photons generated with the linear accelerator traverse healthy tissue before reaching the tumor cells, thereby also affecting the healthy tissue. Moreover, the directing of the high-energy photons to a desired location within the person is not very accurate such that it is difficult to direct the high-energy photons accurately to the location at which the oxygen is generated. This reduces the quality of the radiation treatment.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a radiation application device, a radiation application method and a radiation application computer program for applying radiation to an inner tissue region of a living being, which allow for an improved radiation treatment. It is a further object of the present invention to provide apparatuses and systems comprising the radiation application device.
In a first aspect of the present invention a radiation application device for applying radiation to an inner tissue region of a living being is presented, wherein the radiation application device is adapted to be inserted into the inner tissue region and comprises:
an integrated x-ray source for applying x-rays to the inner tissue region, and an integrated oxygen providing unit for providing oxygen to the inner tissue region.
The x-ray source can directly be inserted into the living being, which is preferentially a person or an animal, at a location at which the inner tissue region is present. In particular, the x-ray source can be inserted directly into or directly adjacent to a tumor region within the living being. The x-rays can therefore very accurately be applied to the inner tissue region. Moreover, since both, the x-ray source and the oxygen providing unit, are integrated in a single radiation application device, the x-rays can very easily and accurately be applied to exactly the inner tissue region, where the oxygen providing unit provides the oxygen, if the radiation application device has been inserted into the inner tissue region. This improves the quality of treating the inner tissue region.
The radiation application device is preferentially an interventional radiation application device, which combines the functionality of radiation generation by the x-ray source and the local in situ application of oxygen to the inner tissue region, which may be a tumor region, for performing an internal radiotherapy, i.e. an internal brachytherapy, wherein the oxygen can be supplied to the inner tissue region such that the oxygenated tissue is in the same area as the area irradiated by the x-rays. This allows applying radiation treatment and oxygen delivery in a synchronized way, wherein the same volume of tissue is targeted.
The x-ray source, which is preferentially a miniature x-ray source, is preferentially adapted to be used for the treatment of solid tumors in situ. It preferentially comprises a cathode, an anode and an intermediate dielectric. The cathode may be, for example, a thermal filament, a field emitting cathode, a Schottky cathode, a piezo- or ferroelectric cathode, or a combination thereof. Optionally, a further electrode, a gate, can be incorporated, for instance, in form of a floating or cathode potential electrostatic lens. The anode can be a reflection or transmission type anode. The x-ray source is preferentially operated with a voltage within the range of 20 to 100 kV, in order to produce spectra in the millimeter to centimeter range in tissue. The operating current is preferentially chosen so as to produce a dose rate being high enough for treating the inner tissue region. The operating current, which can also be regarded as being a tube current, is therefore preferentially within the range of 20 to 800 μΑ. The source can be powered in vivo through, for instance, a miniature high voltage cable, ultrasound et cetera.
It is preferred that the oxygen providing unit is adapted to produce the oxygen by electrolysis of water. In particular, the oxygen providing unit is preferentially adapted to produce the oxygen in situ at the location where the x-rays are applied to the inner tissue region. This allows providing the oxygen directly at the location, at which it is really needed, in a relatively simple way, without necessarily requiring, for instance, an external oxygen storage means like a gas cylinder and a tube for guiding the oxygen from the outside of the living being to the inner tissue region. The oxygen providing unit preferentially comprises an electrolysis electrode for producing the oxygen by the electrolysis of water, wherein the radiation application device is adapted such that in use the electrolysis electrode is contactable with tissue within the living being.
The oxygen providing unit, which is preferentially adapted to produce the oxygen by electrolysis of water, is preferentially integrated with the x-ray source. In particular, the x-ray source may comprise the electrolysis electrode for producing the oxygen by electrolysis of water, wherein the x-ray source is adapted such that in use the electrolysis electrode is contactable with tissue within the living being. The electrolysis electrode may be formed at least partly by the anode, i.e. the x-ray source may be adapted to use the operating current for producing the oxygen in vivo, wherein the x-ray source can be adapted to use the whole operating current or only a part of the operating current for the electrolysis. This allows for a very compact configuration of the x-ray source and the oxygen providing unit, which can lead to a very small combined x-ray source/oxygen providing unit.
In another embodiment the x-ray source comprises a first electrode being a cathode and a second electrode being an anode, wherein the electrolysis electrode is a third electrode. Thus, the radiation application device may comprise, besides the cathode and the anode of the x-ray source, a third electrode, which may be arranged on the surface of the radiation application device or which may form at least a part of the surface of the radiation application device, for performing the electrolysis. Since this further electrode is not used for generating the x-rays, i.e. since the further electrode does not need to be optimized for the generation of x-rays, it can be shaped more freely. This allows configuring the further electrode such that it is optimized for the production of oxygen by water electrolysis, which can lead to a further improved treatment. The electrolysis electrode may be electrically connected to the anode. However, the radiation application device may also be adapted such that a) the voltage at the cathode and/or the anode and b) the voltage at the electrolysis electrode are independently from each other suppliable. Thus, the voltage supply for the x- ray source may be independent of the voltage for the electrolysis electrode. For instance, the radiation application device may comprise an electrical conductor for electrically connecting the electrolysis electrode to a voltage supply outside the living being, wherein this electrical conductor may not electrically connect the anode and/or the cathode to a voltage supply outside of the living being. The radiation application device may therefore comprise an extra electrical conductor, in particular, an extra cable, from the outside for supplying voltage to the electrolysis electrode. This allows optimizing the voltage supply to a) the cathode and/or the anode and b) to the electrolysis electrode independently from each other, which can lead to an improved x-ray application and an improved oxygen generation, which in turn can further improve the radiation treatment.
In a further preferred embodiment the electrolysis electrode is electrically connected to the cathode via a voltage reduction unit for using a reduced voltage for the electrolysis. Thus, the voltage for the electrolysis electrode may be supplied from the internal cathode potential of the x-ray source. The voltage reduction unit may be a voltage divider using a resistor network or another means for reducing the voltage to a life safe low voltage. The same voltage supply may therefore be used for providing the voltage to the cathode and for providing the voltage to the electrolysis electrode, without necessarily requiring two voltage supplies. This can improve the handling of the radiation application device.
It is preferred that the radiation application device comprises an insertion element having a distal tip, wherein the x-ray source and the oxygen providing unit are arranged at the distal tip of the insertion element. In particular, the oxygen providing unit may comprise an electrolysis electrode for producing the oxygen by electrolysis, wherein the x-ray source and the oxygen providing unit are arranged at the distal tip of the insertion element such that in use the electrolysis electrode is contactable with tissue within the living being. For instance, the x-ray source may form the distal point of an insertion element like a needle, for example, a biopsy-like needle, in order to insert the x-ray source, which may comprise an integrated oxygen providing unit, in vivo. This allows placing the x-ray source and the oxygen providing unit accurately within or adjacent to the inner tissue region in a relatively simple way by just placing the tip of the insertion element accordingly. In an embodiment the insertion element is inflatable at the distal tip, wherein the oxygen providing unit comprises an electrolysis electrode arranged on an outside surface of the inflatable distal tip, which may lead to a further improved contact between the electrolysis electrode and the tissue.
The radiation application device may comprise a cooling element for cooling the electrolysis electrode. In particular, if the radiation application device comprises an insertion element having a distal tip, wherein the x-ray source and the oxygen providing unit are arranged at the distal tip of the insertion element such that in use the electrolysis electrode of the x-ray tube is contactable with tissue within the living being, the cooling element may be integrated in the insertion element. The cooling element is therefore preferentially small enough to fit into the insertion element, especially to fit into a needle.
In an embodiment the oxygen providing unit comprises a delivery tube for delivering the oxygen from an outside location, which is outside the living being, to the inner tissue region. Thus, the oxygen may be delivered to the location, where the x-ray source is located within the living being, by using a tube. The delivery tube may be integrated with an insertion element for inserting the x-ray source into the living being. The insertion element may be regarded as being a source applicator for inserting the x-ray source at a desired position within the living being. The delivery tube may therefore be integrated with the source applicator. This allows using a relatively simple x-ray source, without being adapted to perform a water electrolysis, wherein also in this case the x-ray source and the oxygen providing unit, which in this embodiment comprises a delivery tube with a distal opening, can be placed relatively easily within or adjacent to the inner tissue region by placing the tip of the insertion element accordingly.
In another aspect of the present invention a radiation application apparatus for applying radiation to an inner tissue region of a living being is presented, wherein the radiation application apparatus comprises:
- a radiation application device as defined in claim 1, and
a power supply connected to the x-ray source of the radiation application device for powering the x-ray source.
In a further aspect of the present invention a radiation application system for applying radiation to an inner tissue region of a living being is presented, wherein the radiation application system comprises:
a radiation application apparatus as defined in claim 12, and
an imaging apparatus for imaging the radiation application device within the living being. In another aspect of the present invention a radiation application method for applying radiation to an inner tissue region of a living being by using a radiation application device as defined in claim 1, which has been inserted into the living being, is presented, wherein the radiation application method comprises applying x-rays of the x-ray source of the radiation application device to the inner tissue region and providing oxygen by using the oxygen providing unit of the radiation application device to the same inner tissue region. The application of the x-rays and the provision of the oxygen to the same inner tissue region are preferentially performed concurrently.
In a further aspect of the present invention a radiation application computer program for applying radiation to an inner tissue region within a living being by using a radiation application apparatus as defined in claim 12 is presented, wherein the radiation application computer program comprises program code means for causing the radiation application apparatus to carry out the steps of the radiation application method as defined in claim 14, when the radiation application computer program is run on a computer controlling the radiation application apparatus.
It shall be understood that the radiation application device of claim 1, the radiation application apparatus of claim 12, the radiation application system of claim 13, the radiation application method of claim 14, and the radiation application computer program of claim 15 have similar and/or identical preferred embodiments, in particular, as defined in the dependent claims.
It shall be understood that a preferred embodiment of the invention can also be any combination of the dependent claims or above embodiments with the respective independent claim.
These and other aspects of the invention will be apparent from and elucidated with reference to the embodiments described hereinafter.
BRIEF DESCRIPTION OF THE DRAWINGS
In the following drawings:
Fig. 1 shows schematically and exemplarily an embodiment of a radiation application system for applying radiation to an inner tissue region of a living being,
Fig. 2 shows schematically and exemplarily an embodiment of a radiation application device comprising an integrated x-ray source and an integrated oxygen providing unit, Fig. 3 shows a flowchart exemplarily illustrating a radiation application method for applying radiation to an inner tissue region of a living being,
Figs. 4 to 6 and 8 show schematically and exemplarily further embodiments of a radiation application device comprising an integrated x-ray source and an integrated oxygen providing unit, and
Fig. 7 schematically and exemplarily illustrates a voltage reduction unit between a cathode and an electrolysis electrode.
DETAILED DESCRIPTION OF EMBODIMENTS
Fig. 1 shows schematically and exemplarily an embodiment of a radiation application system for applying radiation to an inner tissue region of a living being. In this embodiment the radiation application system is a brachytherapy system 1 for applying x-rays to an inner tumor region 7 within a person 6 lying on a support means like a patient table 8. The brachytherapy system 1 comprises a radiation application apparatus 3 with a radiation application device 4 and a power supply 15 for powering the radiation application device 4. The radiation application device 4 comprises an insertion element 5 having a distal tip 21, wherein a miniature x-ray source for applying x-rays to the inner tumor region 7 is arranged at the distal tip 21 of the insertion element 5. The x-ray source has an integrated oxygen providing unit such that at the distal tip 21 also oxygen can be provided to the inner tissue region 7. In this embodiment the insertion element 5 is a biopsy needle for placing the x-ray source and the oxygen providing unit in vivo within or adjacent to the tumor region 7.
The insertion process can be monitored by using an imaging apparatus 2 for imaging the radiation application device 4 within the person 6. The imaging apparatus 2 comprises an imaging radiation source 9 for generating imaging radiation 10 for traversing the person 6 with the inner tumor region 7. In this embodiment the imaging radiation source 9 is an imaging x-ray tube and the imaging radiation 10 are imaging x-rays. After the imaging radiation 10 has traversed the person 6 with the inner tumor region 7, the imaging radiation 10 is detected by an imaging radiation detector 11 being, in this embodiment, an imaging x-ray detector. The imaging radiation detector 11 provides detection values, which are indicative of the detected imaging radiation, to an imaging control unit 12, which generates projection images based on the received detection values. The projection images are shown to a user like a physician by using a display 13. The imaging radiation source 9 and the imaging radiation detector 11 can be mounted on a C-arm, in order to allow the imaging apparatus 2 to acquire projection images in different projection directions. In other embodiments instead of the imaging apparatus 2, which can also be regarded as being a fluoroscopy apparatus, another imaging apparatus may be used for monitoring the insertion of the insertion element 5 into the inner tumor region 7 within the person 6 like an ultrasound imaging apparatus, an x-ray computed tomography imaging apparatus, a magnetic resonance imaging apparatus, et cetera.
The x-ray source with the integrated oxygen providing unit is schematically and exemplarily illustrated in Fig. 2. The x-ray source 19, which is preferentially adapted to be used for the treatment of solid tumors in situ and preferentially not for the irradiation of tumor cavities like in accelerated partial breast irradiation procedures, comprises a cathode 18, an anode 20 and an intermediate dielectric (not shown in Fig. 2). The cathode 18 is a thermal filament. However, in another embodiment the cathode 18 can also be a field emitting cathode, a Schottky cathode, a piezo-or ferroelectric cathode, or a combination thereof. The anode 20 can be a reflection or transmission type anode. The x-ray source 19 is operated with a voltage within the range of 20 to 100 kV by the voltage supply 15, in order to produce spectra in the millimeter to centimeter range in the tissue. The operating current is preferentially chosen so as to produce a dose rate being high enough to treat the inner tissue region 7, i.e. it is preferentially within the range of 20 to 800 μΑ. The x-ray source 19 is powered in vivo by the voltage supply 15 via a miniature high voltage cable, wherein at the cathode 18 a negative high voltage is applied and the anode 20 and the person 6 are connected to ground.
The anode 20 fulfills two functions, i.e. it is the anode of the x-rays generation process and it is an electrolysis electrode for producing the oxygen by electrolysis of water. In this way the oxygen can be produced in situ at the location where the x-rays are applied to the inner tissue region 7. In order to allow this electrolysis of water, the x-ray source 19 is configured such that the electrolysis electrode 20, i.e. the anode 20, is in contact with the inner tissue region 7 within the person 6, if the tip 21 of the needle 5 has been inserted into the inner tissue region 7. It should be noted that Fig. 2 is just shown for illustrating the integration of the oxygen generation with the x-ray source 19 comprising the cathode 18 and the anode 20 at the tip of the needle and for illustrating the electrical connections, i.e. further details like details of the needle are not shown for clarity reasons.
In the following an embodiment of a radiation application method for applying radiation to an inner tissue region of a living being by using the radiation application device 4 will exemplarily be described with reference to a flowchart shown in Fig. 3. In step 101 the system is initialized and prepared for applying the radiation and providing the oxygen to the tumor tissue region 7. In particular, the distal tip 21 of the needle 5 is inserted into the inner tumor region 7 under guidance of projection images generated by the imaging apparatus 2. In step 102 x-rays are generated by the x-ray source 19 and applied to the inner tumor region 7, while concurrently oxygen is provided by the oxygen providing unit in step 103. In particular, at the anode x-rays are generated and oxygen is produced by electrolysis. After the inner tumor region 7 has been treated, the radiation application method ends in step 104.
In another embodiment, in which the oxygen providing unit and the x-ray source may be independently controllable, the provision of oxygen may be performed immediately before applying the radiation. For instance, steps 102 and 103 may be performed in a loop, wherein within the loop step 102 is performed before step 103.
Although in the above described embodiment the anode of the x-ray source also functions as an electrolysis electrode, in another embodiment the radiation application device may comprise a first electrode being the cathode of the x-ray source, a second electrode being the anode of the x-ray source and a third electrode being the electrolysis electrode, wherein the electrolysis electrode can be electrically connected to the anode. Thus, the radiation application device may comprise, besides the cathode and the anode of the x-ray source, a further electrode on the surface of the radiation application device or forming at least a part of the surface of the radiation application, in particular, on the surface of the tip of the insertion element or forming at least a part of the surface of the tip of the insertion element, for performing the electrolysis as schematically and exemplarily illustrated in Fig. 4.
In Fig. 4 the radiation application device 204 comprises an insertion element 205 having at its distal tip 221 an x-ray source 219 with a cathode 218 and an anode 220, and a third electrode 230 being an electrolysis electrode, wherein the electrolysis electrode 230 is arranged at the outside of the tip 221 such that the electrolysis electrode 230 is contactable with tissue within the person 6. The electrolysis electrode 230 is electrically connected with the anode 220 via an electrical connection 231 like an electrical wire, and the cathode 218 is electrically connected with the power supply 15 via an electrical
connection 250 like a cable.
Although in the embodiment described above with reference to Fig. 4 the electrolysis electrode is arranged at the outside of the tip of the insertion element, in another embodiment the electrolysis electrode can also be arranged at another location at the outside of the insertion element. For instance, as schematically and exemplarily shown in Fig. 5, the radiation application device 304 can comprise an insertion element 305 with an x-ray source, which has a cathode 318 and an anode 320 and which is embedded in insulating material 332, and with a third electrode 330 being an electrolysis electrode circumferentially arranged at an outside side wall of the insertion element 305 close to the tip 321 of the insertion element 305. The electrolysis electrode 330 is electrically connected with the anode 320 via an electrical connection 331 like an electrical wire. The cathode 318 can be connected with the power supply 15 via an electrical connection 350 being, for instance, a cable.
In a further embodiment, which is schematically and exemplarily illustrated in Fig. 6, a radiation application device 404 is adapted such that the voltage at the cathode 418 and the voltage at the electrolysis electrode 430 are suppliable independently from each other. In particular, in this embodiment the radiation application device 404 comprises an electrical conductor 436 for electrically connecting the electrolysis electrode 430 to a voltage supply outside the person, wherein the electrical conductor 430 does not electrically connect the cathode 418 or the anode 420 to a voltage supply outside the person 6. The electrical conductor 430 is an extra cable from the outside for supplying voltage to the electrolysis electrode. Moreover, in this embodiment the insertion element 405 is a balloon insertion element with an inflatable part 434, which is shown in Fig. 6 in an inflated state, wherein the outside of the inflatable part 434 comprises the electrolysis electrode 430. The inflatable part 434 can be inflated by using an external pump and an internal tube 433 within the insertion element 405. Furthermore, in this embodiment the cathode 418 and the anode 420 are electrically connected with the power supply 15 outside of the person 6 via electrical connections 450, 435 being preferentially electrical cables.
Thus, in this embodiment at the tip 421 of the insertion element 405 an integrated x-ray source 419 for applying x-rays to the inner tissue region 7 of the person 6 and an integrated electrolysis electrode 430 forming an integrated oxygen providing unit for providing oxygen to the same inner tissue region 7 are provided. It should be noted that also in other embodiments, which comprise a third electrolysis electrode, like the embodiments described above with reference to Figs. 4 and 5, the electrolysis electrode can be separately supplied by voltage using an extra electrical conductor. However, the electrolysis electrode can also be electrically connected to the cathode via a voltage reduction unit for using a reduced voltage for the electrolysis of the water. A corresponding electrical configuration is schematically and exemplarily illustrated in Fig. 7.
In Fig. 7 an x-ray source 519 and an electrolysis electrode 530 of a radiation application device are shown. The x-ray source 519 comprises a cathode 518 and an anode 520, wherein the electrolysis electrode 530 is electrically connected to the cathode 518 via a voltage reduction unit 540 and wherein the cathode 518 is electrically connected to the power supply 15. In this embodiment the voltage reduction unit 540 is a voltage divider comprising resistors 542, 543.
Fig. 7 just illustrates the electrical configuration of an embodiment with an electrolysis electrode receiving voltage from the cathode of the x-ray source via a voltage reduction unit, i.e. also in this case an insertion element and further elements of the radiation application device, which are not shown in Fig. 7 for clarity reasons, are preferentially present. For instance, the electrical configuration illustrated in Fig. 7 can be used with the embodiments shown in Figs. 4 and 5, if in these embodiments the electrolysis electrode is not electrically connected to the anode, but via a voltage reduction unit with the cathode.
In a further embodiment, which is exemplarily and schematically illustrated in Fig. 8, the radiation application device 604 includes a delivery tube 651 for delivering the oxygen from an outside location, which is outside the person, to the inner tissue region. In this embodiment outside the person 6 an oxygen storage unit like an oxygen gas cylinder and an oxygen control unit may be provided, in order to allow the flow of the oxygen from the outside of the person 6 to the inner tissue region through the delivery tube 651 in a controlled way. The oxygen providing unit may then be formed by the delivery tube 651, especially by the distal opening of the delivery tube. The delivery tube 651 is integrated with an insertion element 605 like a needle for inserting the x-ray source 619 into the person 6. The insertion element 605 may be regarded as being a source applicator for inserting the x-ray source 619 at a desired position within the person 6. Also in this embodiment the x-ray source 619 comprises a cathode 618 with an anode 620, wherein the cathode 618 and the anode 620 are electrically connected with the power supply 15 via electrical connections 650, 635.
In the above described embodiments the electrolysis electrode can be powered such that the electrolysis electrode is not heated to a temperature, which could harm the tissue. However, it is also possible to power the electrolysis electrode such that it is heated to a temperature having a desired therapeutic effect. Moreover, parts of the tip of the insertion element, in particular, the anode of the x-ray tube, may be cooled by using a cooling element. For instance, if in an embodiment oxygen is provided from the outside of the person to the distal tip of the insertion element via a delivery tube, the oxygen may be cooled, in order to cool the distal tip of the insertion element, in particular, the anode of the x-ray source. Thus, the oxygen provision and the cooling can be integrated. However, the cooling effect can also be provided by a separate cooling element like a cooling tube guiding cooling fluid to the distal tip and a further cooling tube for guiding the cooling fluid away from the distal tip, in order to provide a closed cooling loop, particularly if the oxygen is locally produced at the tip of the insertion element by using an electrolysis electrode. The cooling element may also be formed by one or several cooling tubes for guiding the cooling fluid to the distal tip of the insertion element, wherein the distal tip can comprise one or several openings for allowing the cooling fluid to leave the distal tip. In this case the cooling fluid is biocompatible. For example, the cooling fluid may be water.
Tumor hypoxia is a condition involving tumor cell oxygen deprivation. During tumor growth, the blood supply through new capillaries is often lagging, especially in the center of the tumor. Hypoxia reduces the sensitivity of tumor cells to both chemo- and radiotherapy. In the case of radiotherapy, the explanation of this phenomenon involves radiation produced oxygen free radicals as mediator of DNA damage. Oxygenation of tumors as a method of enhancing the treatment efficacy has been investigated for many years.
Systemic methods involve that the patient breathes gas mixtures with increased oxygen concentration. Such treatments are hampered by safety issues due to the high flammability of oxygen and by systemic side-effects like high fewer and asthma. Also, systemic methods lack special control of the oxygenation. As a remedy, an implantable micro-oxygen generator has been suggested for external beam radiotherapy in the above mentioned article. However, this combination of the implantable micro-oxygen generator with the external beam radiotherapy has several drawbacks and complications like the above mentioned difficulty to provide the application of the radiation and the provision of the oxygen accurately at the same location within a living being.
In above described embodiments the radiation application device provides therefore an integration of electrolytical oxygen generation with a miniature tube to be used for electronic brachytherapy. This can make it possible to avoid an extra system for oxygenation and to avoid positioning problems. With the two systems, i.e. radiotherapeutic and oxygen-providing, integrated, they are positioned together and in only one step, for example, by using a stiff biopsy-like needle containing the mini tube.
A simultaneous generation of oxygen locally in the tumor as an integrated part of a miniature x-ray tube inserted into a tumor, which may be a liver, pancreas, prostate, et cetera tumor, may be provided. The miniature x-ray tube may be operated at a modest voltage of, for instance, 50 kV. The advantages include that the tube can be turned off and that the radiation energy is relatively low and thus has a short range. This implies that the treatment does not have to be carried out in, for example, a radiotherapy bunker, but can be given in interventional x-ray facilities and operation rooms. Therefore, radiotherapy is possible in various departments and outpatient settings and the treatment can be given by, for instance, an interventional radiologist. The healthy tissue of the patient and treatment personnel are spared.
In the miniature x-ray tube the applied voltage gives the energy of the radiation, i.e. the maximum energy of the bremsstrahlung spectrum, and thus the radiation range in tissue. An acceleration voltage of 50 kV gives a mean energy of about 25 keV. In most applications the distance to the target tissue is about 0.5 to 4 cm, requiring radiation energy of about 20 to 50 keV. This means that the acceleration voltage of the miniature tube is preferentially between 50 to 100 kV. The tube current, i.e. the operating current, is preferentially in the range of 50 to 500 μΑ.
In above described embodiments the radiation application device comprises a miniature x-ray source for image guided interventional radiotherapy. The miniature source may have an integrated electrolytical production of oxygen for oxygenation of hypoxic tumors simultaneously with the radiation therapy. Part of or the whole tube current can be used for electrolysis of water in vivo. Very small miniature sources may be permanently implanted, similar to the standard low dose rate (LDR) isotopic brachytherapy. This means one or several x-ray sources with integrated oxygen production capability may be
intraoperatively or percutaneously placed into a tumor using, for instance, a syringe and using a wireless power transmission like a wireless ultrasound powering as disclosed, for example, in the above mentioned article.
The electrolysis reaction for generating the oxygen at the electrolysis electrode may be described by following equation: 40H"(aq)→02 (g) + 2H20(l)+ 4e"
At another location, which may be on the outside of the tube, on an applicator, on a clip attached to the person, et cetera, a corresponding reaction, i.e. a reduction, produces H2, which is inert and which may be eliminated via the lungs. In water electrolysis one oxygen molecule requires four electrons. The desired target oxygen concentration is
> 6.4 · 10~5 mol/kg , meaning that 6.4 · 10~8 moloxygen per gram tissue are preferred. Thus, in an embodiment the operating current may be about 200 μιη for 2 min for giving a desired amount of electrons to oxygenate 1 g of tissue. In above described embodiments an electronic brachytherapy system is described comprising a miniature x-ray tube with in situ oxygen generation through water electrolysis. The applications include, but are not limited to, a subgroup of isotopic and electronic brachytherapy applications, for instance, for treatment of prostate, pancreas, liver, rectum, and kidney cancer. In particular, the embodiments may be adapted to be used for a percutaneous brachytherapy where a solid tumor is punctured by a needle containing a miniature x-ray source. Especially for tumors with hypoxic regions the described radiation application device is advantageous. However, the radiation application device can also be adapted for other applications. For instance, since high oxygen levels increase
radiosensitivity, the radiation therapy device can also be adapted to be used for, for example, normoxic tumors or tumor regions.
Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the drawings, the disclosure, and the appended claims.
In the claims, the word "comprising" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality.
A single unit or device may fulfill the functions of several items recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage.
The control of the radiation application apparatus in accordance with the above described radiation application method can be implemented as program code means of a computer program and/or as dedicated hardware. A computer program may be
stored/distributed on a suitable medium, such as an optical storage medium or a solid-state medium, supplied together with or as part of other hardware, but may also be distributed in other forms, such as via the Internet or other wired or wireless telecommunication systems.
Any reference signs in the claims should not be construed as limiting the scope. The invention relates to a radiation application device for applying radiation to an inner tissue region of a living being, particularly for treating tumors in situ. The radiation application device is adapted to be inserted into the inner tissue region and comprises an integrated x-ray source for applying x-rays to the inner tissue region and an integrated oxygen providing unit for providing oxygen to the inner tissue region. Since both, the x-ray source and the oxygen providing unit, are integrated in a single radiation application device, the x-rays can very easily and accurately be applied to exactly the inner tissue region, where the oxygen providing unit provides the oxygen, if the radiation application device has been inserted into the inner tissue region. This improves the quality of treating the inner tissue region.

Claims

CLAIMS:
1. A radiation application device for applying radiation to an inner tissue region of a living being, the radiation application device (4; 204; 304; 404; 604) being adapted to be inserted into the inner tissue region and comprising:
an integrated x-ray source (19; 219; 319; 419; 619) for applying x-rays to the inner tissue region (7), and
an integrated oxygen providing unit (20; 230; 330; 430; 651) for providing oxygen to the inner tissue region (7).
2. The radiation application device as defined in claim 1, wherein the oxygen providing unit comprises an electrolysis electrode (20; 230; 330; 430) for producing the oxygen by electrolysis of water, wherein the radiation application device (4; 204; 304; 404) is adapted such that in use the electrolysis electrode (20; 230; 330; 430) is contactable with tissue within the living being (6).
3. The radiation application device as defined in claim 2, wherein the x-ray source (19) comprises a cathode (18) and an anode (20), wherein the electrolysis
electrode (20) is formed by the anode (20).
4. The radiation application device as defined in claim 2, wherein the x-ray source (219; 319; 419) comprises a first electrode being a cathode (218; 318; 418) and a second electrode being an anode (220; 320; 420), wherein the electrolysis electrode (230; 330; 430) is a third electrode.
5. The radiation application device as defined in claim 4, wherein the electrolysis electrode (230; 330) is electrically connected to the anode (220; 320).
6. The radiation application device as defined in claim 4, wherein the radiation application device (404) is adapted such that a) voltage at the cathode (418) and/or the anode (420) and b) voltage at the electrolysis electrode (430) are independently from each other suppliable.
7. The radiation application device as defined in claim 4, wherein the electrolysis electrode (530) is electrically connected to the cathode (518) via a voltage reduction unit (540) for using a reduced voltage for the electrolysis.
8. The radiation application device as defined in claim 7, wherein the voltage reduction unit (540) is a voltage divider using resistors (542, 543) for reducing the voltage.
9. The radiation application device as defined in claim 1, wherein the radiation application device (4; 204; 304; 404; 604) comprises an insertion element (5; 205; 305; 405; 605) having a distal tip (21; 221; 321; 421 ; 621), wherein the x-ray source (19; 219; 319; 419; 619) and the oxygen providing unit (20; 230; 330; 430; 651) are arranged at the distal tip (21; 221; 321; 421; 621) of the insertion element (5; 205; 305; 405; 605).
10. The radiation application device as defined in claim 9, wherein the insertion element (405) is inflatable at the distal tip (421), wherein the oxygen providing unit comprises an electrolysis electrode (430) arranged on an outside surface of the inflatable distal tip (421).
11. The radiation application device as defined in claim 1, wherein the oxygen providing unit comprise a delivery tube (621) for delivering the oxygen from an outside location, which is outside the living being (6), to the inner tissue region (7).
12. A radiation application apparatus for applying radiation to an inner tissue region of a living being, the radiation application apparatus (3) comprising:
a radiation application device (4; 204; 304; 404; 604) as defined in claim 1, and
- a power supply (15) connected to the x-ray source (19; 219; 319; 419; 619) of the radiation application device for powering the x-ray source (19; 219; 319; 419; 619).
13. A radiation application system for applying radiation to an inner tissue region of a living being, the radiation application system (1) comprising: a radiation application apparatus (3) as defined in claim 12, and an imaging apparatus (2) for imaging the radiation application device (4) within the living being (6).
14. A radiation application method for applying radiation to an inner tissue region of a living being by using a radiation application device as defined in claim 1, which has been inserted into the living being (6), the radiation application method comprising applying x- rays of the x-ray source (19; 219; 319; 419; 619) of the radiation application device (4; 204; 304; 404; 604) to the inner tissue region (7) and providing oxygen by using the oxygen providing unit (20; 230; 330; 430; 651) of the radiation application device (4; 204; 304; 404; 604) to the same inner tissue region (7).
15. A radiation application computer program for applying radiation to an inner tissue region of a living being by using a radiation application apparatus as defined in claim 12, the radiation application computer program comprising program code means for causing the radiation application apparatus (3) to carry out the steps of the radiation application method as defined in claim 14, when the radiation application computer program is run on a computer controlling the radiation application apparatus (3).
PCT/IB2014/060121 2013-03-26 2014-03-25 Radiation application device WO2014155283A1 (en)

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US61/805,238 2013-03-26

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Citations (2)

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